Skip to Content
MDPIMDPI
NutrientsNutrients
PDF
  • Systematic Review
  • Open Access

1 June 2025

Vitamin D in the Transition from Acute to Chronic Pain: A Systematic Review

,
,
,
,
,
,
,
,
and
1
Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
2
Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma University, 00166 Rome, Italy
3
Laboratory of Physiology and Pharmacology of Pain, IRCCS San Raffaele Roma, 00166 Rome, Italy
4
Department of Health Sciences, Institute of Research for Food Safety and Health (IRC-FSH), University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Nutrients2025, 17(11), 1912;https://doi.org/10.3390/nu17111912
This article belongs to the Special Issue Nutrition and Nutraceuticals for Pain Prevention and Treatment
Version Notes
Order Reprints

Abstract

Background: The transition from acute to chronic pain is an important clinical phenomenon that significantly impacts the healthcare system. Despite decades of research, preventing this transition remains a complex challenge. Many studies have explored the various factors that contribute to the development of chronic pain, but the underlying mechanisms are still largely unclear. In this frame, vitamin D (VD) plays an important role in pain mechanism development, with emerging evidence suggesting it influences pain perception, inflammation, and nerve function. Methods: A total of 14 eligible original research articles were identified. Results: Our qualitative analysis showed that VD did not directly influence the transition from acute to chronic pain, but it affected pain intensity, improving outcomes in patients at risk of developing chronic pain. Conclusions: Additional randomized clinical trials, particularly double-blind, placebo-controlled studies, which are regarded as the gold standard in clinical research, are warranted to evaluate the role of vitamin D in the progression from acute to chronic pain

1. Introduction

Chronic pain is still a challenging task in clinical practice. About 30% of adults worldwide suffer from it [1], resulting in a poor quality of life, a higher risk of developing disabilities, and a social impact [2,3]. The therapeutic approach is still aimed at determining which drugs or drug combinations offer the most efficacy with the fewest adverse effects in order to improve patient compliance, even though available treatments often produce insufficient pain relief [4]. The difficulty in the pharmacological management of chronic pain derives from the complexity of the pain neuroaxis [5]. In addition, several cellular and molecular events, such as considerable transcriptional activity, also contribute to persistent pain [6]; thus, pain transmission must be seen as a multifactorial dynamic process. In the absence of disease-modifying therapies and proper symptomatic treatment, preventive measures are crucial. Over the past few years, the process known as the transition from acute to chronic pain has gained increasing attention. It has been proposed that some chronic pain forms could be considered as a progression of acute pain, leading to a shift from physiological to pathological pain [6]. This conceptualization, although not widely accepted [7], suggests that one mechanistic type of pain can evolve into another kind of pain. For instance, acute pain caused by tissue injury and inflammation can develop into neuropathic pain. The development of chronic pain frequently occurs as a side effect of chemotherapy and radiotherapy [8,9] or is associated with surgical tissue trauma. In this case, nerve damage constitutes a significant determinant of this process, but the mechanisms, including those at the cellular and molecular levels, remain to be elucidated. The research focuses on the synaptic [10] and immune [11,12] adaptive responses after end-organ damage as well as on deficits in neuronal energy balance [13,14]. Within this framework, a recent study has demonstrated that N-Acylethanolamine acid amidase (NAAA) acts as a regulatory checkpoint for spinal metabolism, resulting in a significant impact on the pain consolidation process. Notably, this enzyme can be targeted by small-molecule therapeutics with inhibitory activity, thereby paving the way for a novel therapeutic approach in the progression of chronic pain [15]. In the clinical setting, the timely identification of individuals who are prone to developing chronic pain is essential to minimize the risk of the transition into chronic intractable pain. While injury, acute stress events, surgery, metabolic diseases, chemotherapy, and infections are well-established trigger factors [16], the precise timing of transition remains an open question. However, predictive factors such as patient demographics, phenotypic trait variations, acute pain characteristics (i.e., acute pain intensity/severity, duration, and cumulative trauma exposure) [17,18,19], and psychosocial factors [20] have been identified. It is commonly accepted that this process occurs some period after the onset of acute pain. Still, the possibility that both acute and chronic pain mechanisms may arise simultaneously in individuals with persistent pain cannot be ruled out [16]. Another important concern relates to the management of acute pain conditions. Indeed, treatment is largely dependent on a handful of analgesic drug classes, such as opioids, which may lose effectiveness over time and can also lead to addiction. Recently, the literature has placed a significant focus on the interplay between vitamin D (VD) and pain. VD, known as a hormone and neuroactive steroid, can exert analgesic effects by modulating neuronal excitability. The molecular mechanisms by which it interferes with nociceptive processing encompass the inhibition of both nitric oxide synthase and Cox-2 expression, stimulation of 15-prostaglandin dehydrogenase (15-PGDH) expression, and upregulation of transforming growth factor beta in glial cells and macrophage colony-stimulating factor in astrocytes and microglia [21]. Observational studies indicate that hypovitaminosis D is associated with musculoskeletal pain [22], myalgia [23], chronic lower back pain, and chronic headache [24]. Additionally, appropriate VD supplementation, particularly in patients with VD deficiency, can enhance pain relief in several chronic pain conditions [25]. In this systematic review, we examine the impact of VD status and its supplementation in the transition from the acute to chronic pain state in humans. To the best of our knowledge, no existing systematic review or meta-analysis has yet offered a qualitative assessment of the relationship between vitamin D and the process of pain chronification.

2. Methods

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [26] and was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42024563201). A semi-automated methodology was employed using the MySLR platform, available at https://myslr.unical.it (accessed on 1 July 2024). This digital tool simulates human reasoning by utilizing the Latent Dirichlet Allocation (LDA) algorithm for topic modeling [27], a method previously applied in other studies [26,27,28,29].

2.1. Paper Location and Selection

Two independent reviewers (S.I. and D.M.A.-G.) conducted comprehensive literature searches using PubMed, Scopus, and Web of Science to locate peer-reviewed articles published prior to 1 June 2024. This systematic review encompasses clinical research focused on vitamin D (VD) levels in relation to the transition from acute to chronic pain. The search strategy included keywords such as “VD and chronicization pain”, “VD and postoperative pain”, “VD and neuropathic pain”, “chronicization pain and integra-tion of VD”, “VD and chronic pain development”, “VD and “post-surgical pain” OR “postoperative analgesia” OR “post-surgical analgesia” OR “post-operative pain”, “VD and chemotherapy pain”, “VD and pain transition”.

2.2. Study Selection and Data Extraction

Studies were included in the systematic review focusing on the role of VD in the transition of acute pain in chronic pain, which were all published before 1 June 2024.
Types of Study: randomized clinical trials or prospective (cross-sectional), case–control, or longitudinal studies.
The eligibility criteria for including studies in this systematic review were defined as follows: studies that highlighted the transition from acute to chronic pain in relation to the treatment administered, its duration, and the outcomes achieved; studies that were conducted in humans aged 18 years or older that reported on acute or subacute pain and either assessed vitamin D supplementation or reported serum vitamin D levels, provided they included sufficient information on pain assessment scales. Only articles in English and published between 2010 and 2024 were considered.
The following exclusion criteria were applied during the selection process: publications not written in English; reviews, meta-analyses, systematic reviews, letters, conference abstracts, commentaries, book chapters, or proceedings; studies involving animal models or in vitro experiments; research not focused on acute or subacute pain; studies that did not evaluate vitamin D levels; and those lacking essential data, including information on pain assessment scales.
Two authors, S.I. and D.M.A.G., independently screened all titles and abstracts for eligibility. Any disagreements that arose during the selection process were resolved through discussion, with the goal of reaching a consensus. When necessary, a third reviewer (S.N.) was involved. One author (D.M.A.-G.) extracted the data from the included studies and two others (S.I. and S.N.) subsequently verified it.
The extracted data included author names, year of publication, country of study, study design, participant details (sample size, age, and gender), intervention or vitamin D levels, pain-related outcomes, and the main findings.

2.3. Quality Assessment and Risk of Bias Assessment

The risk of bias in the design and analysis of each included study was independently evaluated by two reviewers (D.M.A.-G. and S.I.) using the NIH Study Quality Assessment Tool (accessed 10 June 2023) [27]. When necessary, three additional reviewers (S.N., C.M., and M.C.C.) were consulted to reach a consensus. The evaluation utilized the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, the Quality Assessment Tool for Case–Control Studies, and the Quality Assessment Tool for Controlled Intervention Studies. These instruments, each comprising 12 to 14 questions, are designed to guide the assessment of internal validity by examining factors such as selection bias, methodological rigor, information accuracy, measurement consistency, and potential confounders.

3. Results

3.1. Data Collection

After multiple screening phases, 14 articles addressing vitamin D (VD) levels or VD supplementation during the transition from acute to chronic pain were included in the qualitative analysis (systematic review).
The systematic review identified 2816 records from the literature search. After removing duplicates, 1583 articles were left for further examination. Of these, 1616 were excluded based on their title and 471 articles were excluded by abstract. After screening by title and abstract, 529 articles were considered for full-text eligibility assessment.
A total of 360 articles were excluded from the final database because they were reviews, 37 were excluded because they were in vitro and in vivo studies, and 118 articles were excluded because they were systematic reviews.
Finally, 14 clinical trials involving patients, published between 2010 and 2023, met the eligibility criteria and were included in our review.
The literature search and screening process is detailed in Figure 1.
Figure 1. PRISMA flow diagram illustrating the selection algorithm for eligible studies.

3.2. Characteristics of the Studies Included

Table 1 summarizes the characteristics of studies reporting blood levels of VD and its role in the transition from acute to chronic pain, while Table 2 summarizes those of the studies also reporting VD supplementation. Articles in both tables appear in descending order by year of publication.
Of the fourteen eligible studies, nine observational studies were included: five prospective or retrospective studies, one case–control study, one cross-sectional study, and two longitudinal studies. In addition, five randomized intervention studies were also included. The studies were published from 2010 to 2023 and conducted in seven countries: USA, Europe, China, India, Iran Czech Republic, Poland, Spain, and Hong Kong. The ages of all the participants ranged from 30 to 100 years. Seven studies were conducted in both sexes [30,31,32,33,34,35,36], whereas one study was exclusively conducted in males [37] and five in females [38,39,40,41]. One study did not report the sex [42]. VD levels or supplementation were assessed in several conditions such as pre/post-surgery [30,33,34,35]; patients under chemotherapy, including paclitaxel [32,38,39]; women with an aromatase inhibitor [36,40,41,43]; non-chronic musculoskeletal pain [31,42]; and middle age and elderly subjects [37].
This systematic review included studies that utilized a wide variety of pain test batteries, such as the Numeric Rating Scale (NRS) [30], the Visual Analog Scale (VAS) [31,33,34,35,42,43] for the self-reported level of pain intensity, a 5-point Likert scale [33] for the self-reported level of pain relief, and the Brief Pain Inventory (BPI) Short Form for measuring both pain intensity and pain interference in the patient’s life [36]. The location and duration of pain were assessed using the Painful Sites questionnaire [35] and the McGill Pain Map [29], whereas functional disability was recorded in accordance with the Modified Oswestry Disability Questionnaire (MODQ) [31]. MNSI (Michigan Neuropathy Screening Instrument) [32], WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) [33], and sensory CIPN (chemotherapy induced peripheral neuropathy) were used as disease-specific scales [38,39]. Finally, FIQ (Fibromyalgia Impact Questionnaire) [36], HAQ (Health Assessment Questionnaire—Disability) [36,40,41], and CIPN20 (Chemotherapy-Induced Peripheral Neuropathy Quality of Life questionnaire) were used in several studies to assess the impact of pain in relation to physical function, the extent of the patient’s functional ability, and quality of life, respectively, as reported in Table 1 and Table 2.
Table 1. Characteristics of the studies included.
Table 1. Characteristics of the studies included.
Study/
Year		Type of StudyCountryPopulationMean, Age, Years (SD/IC)SexnIntervention/
Duration		Levels of VDPain
Test Used
Chen et al., 2023
[38]		Prospective-retrospective studyUSAPatients with early-stage breast cancer with paclitaxel51.1 y ± 9.9F1191NR1.57 (1.14–2.15) ICSensory CIPN
Zeng et al., 2022
[30]		Retrospective cohort studyChina Patients who underwent elective non-cardiac thoracic surgeryGroup 1
57.5 y ± 13.1
Group 2
58.8 y ± 11.8		F = 74
M = 61		135
Group 1 = 73
Group 2 = 62		3 monthsGroup 1 low 25(OH)D levels (<30 nmol/L)
Group 2 25(OH)D levels (>30 nmol/L)		Pain scores (numerical rating scale)
Hao-Wei et al., 2021 [42]Cross-sectional studyChinaNon-specific acute lower back pain (Ns-ALCP) and non-specific-chronic lower back pain patients (Ns-CLBP)63.42 ± 11.26 years, with a range of 33 to 80 years.NR198
Ns-ALCP = 60
Ns-CLBP = 78
Control = 60		NRNs-ALBP
21.44 ± 8.46
Ns-CLBP
18.25 ± 8.05
(ng/mL)
Control
25.70 ± 10.04		VAS scale
Jennaro et al., 2020
[39]		Prospective observation clinical studyUSAPatients with stage I–III breast cancer receiving weekly paclitaxel47.6 y (28–59 IC)
54.6 y (34–71 IC)		F37Duration 12 weeksVD deficiency (defined as <20 ng/mL) was identified in 41% (15/37) of assessed patientsCIPN20
Panwar et al., 2018
[31]		Prospective, observational, triple arm, case and control studyIndiaPatients with lower back pain of duration ≥ 6 weeks (CLBP), patients with subacute lower back pain (SLBP)
and controls.		CLBP 40.40 y ± 13.638
SLBP
40.69 y ± 14.469
Control
37.95 y ± 15.255		CLBP
M = 104
F = 146
SLBP
M = 82
F = 95
Control
M = 112
F = 136		675
CLBP = 250
SLBP = 177
Control = 248		3 monthsCLBP
20.36 ± 12.569
SLBP
21.42 ± 13.209
Controls
20.84 ± 6.931		BMcGill Pain Map
VAS scale
MODQ
Grim et al., 2017
[32]		Case and control Czech RepublicPatients with breast carcinoma from the undergoing chemotherapy based on 80 mg/m2 paclitaxel on a weekly basis (12 cycles)56 y ± 12.2M = 10%
F = 90% 		70Duration 12 weeks
Evaluation 1
after 4 weeks
Evaluation 2
End treatment 12 weeks		Before chemotherapy
Without NP 38.08 ± 15.6 nmol/L
With NPz 26.94 nmol/L ± 8.5
During chemotherapy (4 week)
Without NP 37.44 nmol/L ± 19.9
With NP 24.28 nmol/L ± 8.9
After chemotherapy (12 week)
Without NP 42.33 nmol/L ± 9.6
With NP 31.4 nmol/L ± 10.4		MNSI
McCabe et al., 2016
[37]		Multicenter/longitudinal studyEurope Population sample of middle age and elderly menaged 40–79M2736Participants were invited to attend repeat assessment after a mean interval of 4.3 years (range 3–5.7 years).25(OH)D–quintiles (ng/mL)
1. ≥36.3
2. 26.7–36.2
3. 20.7–26.6
4. 15.6–20.6
5. <15.6
25(OH)2D–quintiles (pg/mL)
1. ≥72.5
2. 62.2–72.5
3. 55.2–62.0
4. 45.4–55.0
5. <45.4		Painful sites
Lee et al., 2015
[33]		Longitudinal cohort studyHong Kong Patients after surgery knee arthroplasty62–73 yF = 153
M = 61		2143 months25(OH)D levels
<30 nmol/L
>30 nmol/L–<50 nmol/L
>50 nmol/L		Pain scale WOMAC
EQ-5D-VAS
Abbreviations: CIPN, chemotherapy-induced peripheral neuropathy; CIPN20, 20-item Quality of Life Questionnaire for Chemotherapy-Induced Peripheral Neuropathy; CLBP, chronic lower back pain; EQ-5D-VAS, EuroQol 5-Dimension Visual Analog Scale; IC, interquartile range; MNSI, Michigan Neuropathy Screening Instrument; MODQ, Modified Oswestry Disability Questionnaire; NR, not reported; Ns-ALBP, non-specific acute lower back pain; Ns-CLBP, non-specific chronic lower back pain; SLBP, subacute lower back pain; VAS, Visual Analog Scale; VD, vitamin D; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.
Table 2. Characteristics of the studies included.
Table 2. Characteristics of the studies included.
Study/YearType of StudyCountryPopulationMean, Age, Years (SD/IC)SexnIntervention/
Duration		Levels of VDPain
Test Used
Melika et al., 2019
[34]		Randomized clinical trialIranAdult patients with diagnosed brain tumor with serum level of 25 (OH) VD ≤ 20 ng/dLVD
48.2 ± 15.3 y
PL 44.3 ± 15.2 y		M = 30
F = 30		60
VD = 30
PL = 30		300,000 IU VD 2- to 14-day interval
before surgery		Preoperatory
VD = 15.9 ± 3.8
PL = 14.5 ± 3.6		VAS scale
Krasowska et al., 2019
[35]		Double-blind randomization studyPolandPatients undergoing posterior lumbar interbody fusion (PLIF) followed by rehabilitation.VD
41.92 ± 2.97
PL
47.33 ± 2.15		VD
M = 9
F = 9
PL
M = 9
F = 12		39
VD = 18
PL = 21		VD (3200 IU dose of VD/day for 5 weeks) and placebo group (PL)The initial serum 25(OH)D3 (nmol/L) VD 46.63 ± 1.69
PL 55.71 ± 4.11
after 5 weeks VD 75.03 ± 3.03 PL 53.62 ± 3.07
After surgery
VD normal
PL decrease levels		VAS scale
Niravath et al. (2019)
[40]		Randomized control trialUSAPost-menopausal women who were beginning adjuvant aromatase inhibitor therapy64 y
(44–82 y)		F = 9393
High dose = 46
Standard dose = 47		Standard-dose VD3 (800 IU daily for 52 weeks), or high-dose VD3 (50,000 IU weekly for 12 weeks, followed by 2000 IU daily for 40 weeks)Baseline vitamin D levels averaged 24.2 ng/mL in the standard-dose group and 21.7 ng/mL in the high-dose group. After 12 weeks, levels rose to 29.3 ng/mL and 50 ng/mL, respectively.HAQ-II
Prieto-Alhambra et al. (2011) [43]Prospective cohort studySpainWomen with breast cancer who were women starting aromatase inhibitor therapyVD < 30 ng/mL
2.63 (8.77)
VD > 30 ng/mL
60.20 (9.64)		F 284
VD < 30 ng/mL =
251
VD > 30 ng/mL = 33		All received daily VD (800 IU) with calcium. Women with baseline VD concentration < 30 ng/mL also received 16,000 IU of D3 orally every 2 weeks.
3 months		Following baseline assessment, 89.7% (260 participants) were vitamin D deficient (<30 ng/mL), with 18.5% (48 individuals) showing severe deficiency (<10 ng/mL)VAS scale
Rastelli et al. (2011)
[36]		Randomized control trialUSAPatients with musculoskeletal pain in women receiving adjuvant anastrozole improves aromatase inhibitor61.5 (8.4)F = 57%57
VD = 28
PL = 29		50,000 IU VD2 weekly for 8 weeks then monthly for 4 months; or 50,000 IU VD2 weekly for 16 weeks then monthly for 2 months.Stratum A = 20–29 ng/mL
Stratum B = 10–19 ng/mL		BPI-SF
FIQ
HAQ-DI
Khan et al. (2010)
[41]		Randomized, placebo-controlled trialUSAWomen with early-stage, receptor-positive, invasive breast cancer who were candidates for adjuvant aromatase inhibitor therapyMean age 56 yF = 6060Group 1: VD (high dose)
Group 2 (control): VD (standard dose)
50,000 IU of VD weekly (16 weeks)		<40 ng/mL vit D = 47
>40 ng/mL vit D = 13		HAQII
Abbreviations: 25(OH)D, 25-hydroxyvitamin D; BPI-SF, Brief Pain Inventory–Short Form; FIQ, Fibromyalgia Impact Questionnaire; HAQ-DI, Health Assessment Questionnaire–Disability Index; HAQ-II, Health Assessment Questionnaire II; IC, interquartile range; PL, placebo; PLIF, posterior lumbar interbody fusion; VAS, Visual Analog Scale; VD, vitamin D; VD2, vitamin D2.

3.3. Quality Assessment and Risk of Bias Assessment

The risk of bias assessment is summarized in Figure 2A–C. As mentioned above, we used three tools: the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies (n = 8), the Quality Assessment of Case–Control Studies (n = 1), and the Quality Assessment of Controlled Intervention Studies (n = 5). Using these tools, out of the fourteen studies included in the systematic review, two studies were rated as “good” [33,36] and twelve as “fair” [30,31,32,34,35,37,38,39,40,41,42,43,44]. Among the eight observational cohort and cross-sectional studies (Figure 2A), all demonstrated strengths in defining their research questions and outcome measures; however, several lacked reporting on key elements such as participation rates and follow-up adequacy, indicating potential risk of bias. The single case–control study [32] (Figure 2B) was generally well conducted but showed weaknesses in reporting on population clarity and confounding controls. The five controlled intervention studies (Figure 2C) varied in quality, with some showing solid randomization and outcome measurement practices, while others lacked detailed reporting on method of randomization, blinding, allocation concealment, and participant retention. Overall, these findings suggest a moderate risk of bias across most included studies, primarily due to insufficient reporting and methodological limitations.
Figure 2. (A) Summary of risk-of-bias assessment according to the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies (NIH, 2014) [30,31,33,37,38,39,42,43]. (B) Summary Quality Assessment of Case–Control Studies [32]. (C) Summary Quality Assessment according to Health Quality Controlled Intervention Studies (NIH, 2014) [34,35,36,40,41]. The quality rating is 0 for poor (0–4 out of 14 questions), 1 for fair (5–9 out of 14 questions), or 2 for good (>10 out of 14 questions). NR: not reported; created with BioRender (https://www.biorender.com/ accessed on 1 July 2024).

3.4. Topic Identification

The LDA algorithm enabled us to identify two topics related to VD during the transition from acute to chronic pain, which are presented in this section. We develop the discussion starting from Topic 1, as it deals with the impact of VD levels, and then treat Topic 2, which is more specific, as it examines the influence of VD supplementation.

3.4.1. Topic 1: VD Levels and Its Relationship with Transition from Acute to Chronic Pain

This topic includes eight studies, the majority of which are observational in nature, including cross-sectional, prospective, retrospective, cohort, and case–control designs [30,31,32,33,37,38,39,42]. These studies examined the association between circulating levels of vitamin D (VD) and pain conditions, specifically focusing on whether VD deficiency or insufficiency may influence the transition from acute to chronic pain. Conditions explored include postoperative pain, chemotherapy-induced peripheral neuropathy (CIPN), chronic lower back pain, and chronic widespread pain.
By examining the top 30 most significant terms and their frequency within the eight papers categorized under this topic, it became apparent that the fundamental aspect of Topic 1 was the relationship between VD blood/serum levels and acute, subacute, or chronic pain conditions. These studies aim to understand whether higher or insufficient levels of VD could potentially affect the process of chronitization of pain in conditions frequently associated with the transition from acute to chronic pain. Studies clustered in Topic 1 and their main results are summarized in Table 3.
Table 3. List of papers clustered in Topic 1.

3.4.2. Topic 2: The Impact of VD Supplementation on the Transition from Acute to Chronic Pain

This topic includes six studies that investigated the effects of vitamin D (VD) supplementation on the progression from acute to chronic pain and associated outcomes. Five of the studies were randomized controlled trials (RCTs) [34,35,36,40,41], while one, by Prieto-Alhambra et al. [43], was an observational prospective cohort study.
VD supplementation was observed to have a positive effect on quality of life and a reduction in pain [45]. Studies clustered in Topic 2 and their main results are summarized in Table 4. These studies examined various clinical settings, such as post-operative pain, aromatase inhibitor-induced arthralgia, and musculoskeletal pain. All included studies monitored serum VD levels throughout the intervention period.
Table 4. List of papers clustered in Topic 2.

4. Discussion

The mechanisms underlying pain chronification are multifactorial and complex, encompassing inflammatory and neuropathic processes as well as genetics and mental status [46,47]. Theoretically, preventing or reversing the pathological changes during the transition from acute to chronic pain has the potential to prevent or minimize the development of chronic pain. Although any painful condition can lead to the chronification of pain, it is particularly common with surgical trauma [48], lower back pain [17,49,50], and osteoarthritis [51]. Several attempts have been made to develop an analgesic approach to prevent this transition, but available evidence is limited so far [52]. Monotherapy often leads to insufficient therapeutic response; in addition, treating acute pain aggressively to avoid persistent pain is not without risks, such as the occurrence of side effects, the unneeded use of opioids, and the risk of chronic opioid use [7]. Compelling evidence has shown the potential of VD in exerting an influence on pain manifestation, thereby playing a role in the etiology and maintenance of chronic pain states and associated comorbidities [53]. VD is also thought to be of clinical benefit in treating chronic pain without the side effects of currently available analgesics, although its efficacy in specific pain conditions needs further investigation [52,53,54]. The purpose of this systematic review was to summarize the available clinical evidence on the impact of VD in the pain transition process and to evaluate the use of VD supplementation as a potential strategy in preventing or limiting the pain chronification process. In this frame, Zeng et al. demonstrated that low VD levels among patients undergoing video-assisted thoracoscopic surgery are associated with increased moderate to severe postoperative pain within 48 h compared to those with sufficient VD levels [30], while no significant differences in static or dynamic pain scores were detected at 3 months after surgery. In addition, a study conducted by Lee et al. found that nearly half of the patients undergoing knee arthroplasty had low preoperative VD levels, which were associated with increased pain intensity [33]. Lower VD levels did not influence morphine consumption or the quality of postoperative recovery compared to patients with sufficient VD levels. However, patients with VD deficiency may be more prone to experiencing more severe acute and chronic persistent pain after surgery [33], suggesting a possible role of this hormone as a predictive marker of pain intensity. In this context, promising results have been reported by Melika et al., showing that patients exposed to VD for a longer time before the operative time had an insignificantly lower pain score after craniotomy [34]. In addition, Krasowska and colleagues report that supplementation with VD enhanced the reduction in systemic inflammation markers, and when combined with surgery and early postsurgical rehabilitation it may decrease the intensity of pain in LBP patients undergoing PLIF [35]. Results on the increase in pain intensity linked to VD deficiency have also been reported in patients with acute and chronic non-specific LBP by Hao-Wei et al. However, the authors did not rule out a possible role of VD in the transition from acute LBP to chronic LBP owing to the hormone’s well-established effect on neuroplasticity [42]. Although VD insufficiency did not directly influence the transition from acute to chronic pain, the evidence that it affects pain intensity is clinically relevant. In chirurgical settings, pain intensity represents a risk factor for chronicity [48], and the pharmacological approach to controlling acute postoperative pain involves aggressive therapy encompassing the administration of a systemic opioids, non-steroidal anti-inflammatory drugs, and the delivery of local anesthetic to peripheral afferents supplying the chirurgical field. Acute to chronic pain transition may also occur as an adverse effect of chemotherapy [55]. Up to 70% of patients who underwent therapy with paclitaxel developed so-called chemotherapy-induced peripheral neuropathy (CIPN), which profoundly affects the quality of life [52,55]. Of note, around 30% of patients will still have CIPN a year or more after finishing chemotherapy [38]. In this population, VD deficiency did not affect the pain chronification process but rather represents a potential risk factor for both developing CIPN and severe pain [32,38,39]. By contrast, conflicting results have been reported in joint arthralgia related to aromatase inhibitor therapy. Indeed, Niravath et al. showed no significant beneficial effects of high-dose VD supplementation for pain development prevention in this clinical setting [40]. By contrast, Khan et al. found that higher VD levels (> 66 ng/mL) correlated with less joint pain and disability in patients who underwent aromatase inhibitor therapy [41]. Similarly, other studies have also shown some benefits of high-dose VD replacement [35]. Rastelli et al. reported that pain decreased significantly at 2 months in the VD group compared to placebo. The effect on pain was not observed at 4 and 6 months when the majority of subjects were switched from weekly to monthly VD supplementation [36]. In addition, Prieto-Alhambra et al. concluded that a target concentration of 40 ng/mL VD may prevent the development of aromatase-induced arthralgia, but higher loading doses are required to attain this level in women with a deficiency at baseline [43]. It is worth noting that this threshold exceeds the target of 20 ng/mL recommended by the 2010 Institute of Medicine (IOM) report [54]. Although the results of the current systematic review have been mixed, the studies underscore the multifaceted role of VD in various pain conditions, including acute and subacute lower back pain (LBP), chronic widespread pain (CWP), chemotherapy-induced peripheral neuropathy (CIPN), and aromatase inhibitor-induced arthralgia. However, it is important to note that large-scale randomized controlled trials have not consistently supported a benefit of VD supplementation on pain outcomes. For example, the VITAL-Pain ancillary study to the VITAL trial evaluated the effect of long-term supplementation with vitamin D (2000 IU/day) and omega-3 fatty acids (1 g/day) in over 19,000 older adults. The study found no significant reduction in pain prevalence or severity after a median follow-up of 5.3 years, compared to placebo [56]. These findings suggest that while observational and small-scale studies may indicate a potential role of VD in pain modulation, supporting the view that the role of high levels of vitamin D prevents chronic disease [57], the clinical impact of supplementation, particularly at moderate doses, remains uncertain in the general aging population. This further emphasizes the need to tailor interventions based on specific patient characteristics, baseline VD levels, and the etiology of pain. Nevertheless, maintaining adequate VD levels may still offer benefits in managing pain or reducing its intensity across various clinical contexts, which are themselves risk factors for the transition from acute to chronic pain. Further research is warranted to clarify VD’s role in pain management and to determine whether targeted supplementation can meaningfully influence the incidence or severity of painful conditions.

Limitation of the Study

This study has several limitations that must be acknowledged. The majority of the included studies are observational in nature and therefore susceptible to inherent biases. First, the inability to control for all potential confounding factors, such as physical activity, comorbidities, diet, and socioeconomic status, may have introduced bias. Second, reverse causation cannot be ruled out, particularly in cross-sectional studies, where pain conditions might lead to reduced sun exposure and subsequent vitamin D deficiency. Third, differences in serum vitamin D assay methods and pain assessment tools may affect the reliability and comparability of findings across studies. Additionally, significant heterogeneity exists among the included studies in terms of study design, outcome measures, and the populations examined. This variability further limits the ability to synthesize findings and draw consistent conclusions. Although observational data suggest a potential association between vitamin D status and pain outcomes, a direct causal relationship has not been established. The current findings are hypothesis-generating and highlight the need for well-designed, high-quality randomized controlled trials (RCTs) to determine whether vitamin D plays a role in preventing or mitigating the transition from acute to chronic pain. Moreover, a major limitation of this review is the limited number of studies that specifically investigate vitamin D in the context of the transition from acute to chronic pain. This scarcity of data precluded the performance of a meta-analysis.

5. Conclusions

The transition from acute to chronic pain is a complex and multifactorial event involving various pathophysiological changes and is influenced by factors such as individual susceptibility, the duration and intensity of the initial pain, and the effectiveness of therapeutic approaches. In this scenario, VD emerges as a potential pain modulator, with evidence suggesting a role in reducing the intensity of acute pain and preventing some forms of persistent pain. Our qualitative analysis indicated that VD deficiency is related to increased postoperative pain intensity and a greater propensity to develop chronicity in conditions such as lower back pain, arthrosis, and chemotherapy neuropathy. However, its direct involvement in the transition from acute to chronic pain remains controversial. Despite the discrepancies, it is essential to assess the status of VD in patients at risk and consider its integration as part of a multimodal therapeutic strategy, especially in surgical settings. In this context, a preexisting VD deficiency is associated with a higher risk of persistent post-surgical pain, thus favoring its chronification. Further randomized clinical trials (i.e., double-blind and placebo-controlled, considered the “gold standard” of clinical studies) to assess VD and its influence on the transition from acute to chronic pain are warranted.

Author Contributions

Conceptualization, M.C.C., C.M., D.M.A.-G. and S.I.; data curation S.N. and S.I.; writing—original draft preparation, D.M.A.-G. and S.I.; writing—review and editing, S.N. and E.C.; visualization, E.C., R.C., V.M., L.G. and L.C.P.; supervision, M.C.C. and C.M. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by PRIN 2022 cod. 202273HF8 and PRIN 2022 PNRR cod. P2022FAS5R. This study is also supported by the Italian Ministry of Health [Ricerca Corrente].

Data Availability Statement

All data generated/analyzed throughout this research are included in this article.

Acknowledgments

In developing this work, the author(s) utilized AI-based tools to improve language clarity and identify potential issues with phrasing. Following this process, the author(s) reviewed and defined the content as needed and assumed full responsibility for the final version of the publication.

Conflicts of Interest

The authors declare no known conflicting financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Abbreviation

VDVitamin D
MySLRMy Systematic Literature Review
LDALatent Dirichlet Allocation (algorithm for topic modeling)
NRSNumeric Rating Scale
VASVisual Analog Scale
BPIBrief Pain Inventory
BPI-SFBrief Pain Inventory–Short Form
MODQModified Oswestry Disability Questionnaire
MNSIMichigan Neuropathy Screening Instrument
WOMACWestern Ontario and McMaster Universities Osteoarthritis Index
CIPNChemotherapy-induced peripheral neuropathy
CIPN20Chemotherapy-Induced Peripheral Neuropathy 20-item Quality of Life Questionnaire
FIQFibromyalgia Impact Questionnaire
HAQHealth Assessment Questionnaire
HAQ-DIHealth Assessment Questionnaire–Disability Index
AIAromatase inhibitor
AIMSSAromatase Inhibitor-Associated Musculoskeletal Symptom
PLPlacebo
IUInternational Units
25(OH)D25-hydroxyvitamin D (a marker for Vitamin D status)
NPNeuropathic pain
CWPChronic widespread pain
NAAAN-Acylethanolamine acid amidase
SRESummary Risk of Bias Evaluation

References

  1. Cohen, S.P.; Vase, L.; Hooten, W.M. Chronic pain: An update on burden, best practices, and new advances. Lancet 2021, 397, 2082–2097. [Google Scholar] [CrossRef] [PubMed]
  2. Ilari, S.; Nucera, S.; Passacatini, L.C.; Scarano, F.; Macrì, R.; Caminiti, R.; Ruga, S.; Serra, M.; Giancotti, L.A.; Lauro, F.; et al. Exploring the Role of Bergamot Polyphenols in Alleviating Morphine-Induced Hyperalgesia and Tolerance through Modulation of Mitochondrial SIRT3. Nutrients 2024, 16, 2620. [Google Scholar] [CrossRef]
  3. Ilari, S.; Nucera, S.; Passacatini, L.C.; Caminiti, R.; Mazza, V.; Macrì, R.; Serra, M.; Scarano, F.; Malafoglia, V.; Palma, E.; et al. SIRT1: A likely key for future therapeutic strategies for pain management. Pharmacol. Res. 2025, 213, 107670. [Google Scholar] [CrossRef]
  4. Marcianò, G.; Siniscalchi, A.; Di Gennaro, G.; Rania, V.; Vocca, C.; Palleria, C.; Catarisano, L.; Muraca, L.; Citraro, R.; Evangelista, M.; et al. Assessing Gender Differences in Neuropathic Pain Management: Findings from a Real-Life Clinical Cross-Sectional Observational Study. J. Clin. Med. 2024, 13, 5682. [Google Scholar] [CrossRef]
  5. Costigan, M.; Scholz, J.; Woolf, C.J. Neuropathic pain: A maladaptive response of the nervous system to damage. Annu. Rev. Neurosci. 2009, 32, 1–32. [Google Scholar] [CrossRef]
  6. Borsook, D.; Youssef, A.M.; Simons, L.; Elman, I.; Eccleston, C. When pain gets stuck: The evolution of pain chronification and treatment resistance. Pain 2018, 159, 2421–2436. [Google Scholar] [CrossRef]
  7. Finnerup, N.B.; Nikolajsen, L.; Rice, A.S.C. Transition from acute to chronic pain: A misleading concept? Pain 2022, 163, e985–e988. [Google Scholar] [CrossRef]
  8. Paice, J.A. Chronic treatment-related pain in cancer survivors. Pain 2011, 152, S84–S89. [Google Scholar] [CrossRef]
  9. Ilari, S.; Lauro, F.; Giancotti, L.A.; Malafoglia, V.; Dagostino, C.; Gliozzi, M.; Condemi, A.; Maiuolo, J.; Oppedisano, F.; Palma, E.; et al. The Protective Effect of Bergamot Polyphenolic Fraction (BPF) on Chemotherapy-Induced Neuropathic Pain. Pharmaceuticals 2021, 14, 975. [Google Scholar] [CrossRef]
  10. Basbaum, A.I.; Bautista, D.M.; Scherrer, G.; Julius, D. Cellular and molecular mechanisms of pain. Cell 2009, 139, 267–284. [Google Scholar] [CrossRef]
  11. Ji, R.-R.; Chamessian, A.; Zhang, Y.-Q. Pain regulation by non-neuronal cells and inflammation. Science 2016, 354, 572–577. [Google Scholar] [CrossRef] [PubMed]
  12. Marchand, F.; Perretti, M.; McMahon, S.B. Role of the immune system in chronic pain. Nat. Rev. Neurosci. 2005, 6, 521–532. [Google Scholar] [CrossRef]
  13. Joseph, E.K.; Levine, J.D. Mitochondrial electron transport in models of neuropathic and inflammatory pain. Pain 2006, 121, 105–114. [Google Scholar] [CrossRef]
  14. Bennett, G.J.; Doyle, T.; Salvemini, D. Mitotoxicity in distal symmetrical sensory peripheral neuropathies. Nat. Rev. Neurol. 2014, 10, 326–336. [Google Scholar] [CrossRef]
  15. Fotio, Y.; Jung, K.-M.; Palese, F.; Obenaus, A.; Tagne, A.M.; Lin, L.; Rashid, T.I.; Pacheco, R.; Jullienne, A.; Ramirez, J. NAAA-regulated lipid signaling governs the transition from acute to chronic pain. Sci. Adv. 2021, 7, eabi8834. [Google Scholar] [CrossRef]
  16. Price, T.J.; Basbaum, A.I.; Bresnahan, J.; Chambers, J.F.; De Koninck, Y.; Edwards, R.R.; Ji, R.-R.; Katz, J.; Kavelaars, A.; Levine, J.D.; et al. Transition to chronic pain: Opportunities for novel therapeutics. Nat. Rev. Neurosci. 2018, 19, 383–384. [Google Scholar] [CrossRef]
  17. Stevans, J.M.; Delitto, A.; Khoja, S.S.; Patterson, C.G.; Smith, C.N.; Schneider, M.J.; Freburger, J.K.; Greco, C.M.; Freel, J.A.; Sowa, G.A. Risk factors associated with transition from acute to chronic low back pain in US patients seeking primary care. JAMA Netw. open 2021, 4, e2037371. [Google Scholar] [CrossRef]
  18. Friedman, B.W.; Abril, L.; Naeem, F.; Irizarry, E.; Chertoff, A.; McGregor, M.; Bijur, P.E.; Gallagher, E.J. Predicting the transition to chronic pain 6 months after an emergency department visit for acute pain: A prospective cohort study. J. Emerg. Med. 2020, 59, 805–811. [Google Scholar] [CrossRef]
  19. Snyder, D.L.; Girgis, G.; Abd-Elsayed, A. Perioperative Pain Management-Introduction. In Perioperative Pain Management: A Clinical Guide; Springer: Cham, Switzerland, 2024; pp. 3–6. [Google Scholar]
  20. Hruschak, V.; Cochran, G. Psychosocial predictors in the transition from acute to chronic pain: A systematic review. Psychol. Health Med. 2018, 23, 1151–1167. [Google Scholar] [CrossRef]
  21. Habib, A.M.; Nagi, K.; Thillaiappan, N.B.; Sukumaran, V.; Akhtar, S. Vitamin D and its potential interplay with pain signaling pathways. Front. Immunol. 2020, 11, 820. [Google Scholar] [CrossRef]
  22. Alonso-Pérez, J.L.; Martínez-Pérez, I.; Romero-Morales, C.; Abuín-Porras, V.; López-Bueno, R.; Rossettini, G.; Leigheb, M.; Villafañe, J.H. Relationship Between Serum Vitamin D Levels and Chronic Musculoskeletal Pain in Adults: A Systematic Review. Nutrients 2024, 16, 4061. [Google Scholar] [CrossRef] [PubMed]
  23. Kumar, A.; Gopal, H.; Khamkar, K.; Prajapati, P.; Mendiratta, N.; Misra, A.; Vaidya, B.; Abrol, A. Vitamin D deficiency as the primary cause of musculoskeletal complaints in patients referred to rheumatology clinic: A clinical study. Indian J. Rheumatol. 2012, 7, 199–203. [Google Scholar] [CrossRef]
  24. Prakash, S.; Rathore, C.; Makwana, P.; Dave, A.; Joshi, H.; Parekh, H. Vitamin D Deficiency in Patients with Chronic Tension-Type Headache: A Case-Control Study. Headache J. Head Face Pain 2017, 57, 1096–1108. [Google Scholar] [CrossRef]
  25. Helde-Frankling, M.; Björkhem-Bergman, L. Vitamin D in Pain Management. Int. J. Mol. Sci. 2017, 18, 2170. [Google Scholar] [CrossRef]
  26. Radbakhsh, S.; Abrego-Guandique, D.M.; Bacchetti, T.; Aghaee-Bakhtiari, S.H.; Mahmoudi, A.; Manteghi, A.A.; Bazyari, M.J.; Cione, E.; Ferretti, G.; Sahebkar, A. Direct hybridization and bioinformatics analysis of circulating microRNAs in patients with Alzheimer’s disease under intravenous trehalose treatment. Brain Res. 2025, 1857, 149607. [Google Scholar] [CrossRef]
  27. Saraceno, G.F.; Abrego-Guandique, D.M.; Cannataro, R.; Caroleo, M.C.; Cione, E. Machine Learning Approach to Identify Case-Control Studies on ApoE Gene Mutations Linked to Alzheimer’s Disease in Italy. BioMedInformatics 2024, 4, 600–622. [Google Scholar] [CrossRef]
  28. Abrego-Guandique, D.M.; Bonet, M.L.; Caroleo, M.C.; Cannataro, R.; Tucci, P.; Ribot, J.; Cione, E. The Effect of Beta-Carotene on Cognitive Function: A Systematic Review. Brain Sci. 2023, 13, 1468. [Google Scholar] [CrossRef]
  29. Abrego-Guandique, D.M.; Saraceno, G.F.; Cannataro, R.; de Burnside, M.M.; Caroleo, M.C.; Cione, E. Apolipoprotein E and Alzheimer’s Disease in Italian Population: Systematic Review and Meta-Analysis. Brain Sci. 2024, 14, 908. [Google Scholar] [CrossRef]
  30. Zeng, X.; Chen, X.; Li, C.; Shi, H. Preoperative Vitamin D Level is Associated with Acute Pain After Video-Assisted Thoracoscopic Surgery: A Retrospective Cohort Study. J. Pain Res. 2022, 15, 3189–3196. [Google Scholar] [CrossRef]
  31. Panwar, A.; Valupadas, C.; Veeramalla, M.; Vishwas, H.N. Prevalence of vitamin D deficiency in chronic and subacute low back pain patients in India: A triple-arm controlled study. Clin. Rheumatol. 2018, 37, 1367–1374. [Google Scholar] [CrossRef]
  32. Grim, J.; Ticha, A.; Hyspler, R.; Valis, M.; Zadak, Z. Selected risk nutritional factors for chemotherapy-induced polyneuropathy. Nutrients 2017, 9, 535. [Google Scholar] [CrossRef] [PubMed]
  33. Lee, A.; Chan, S.K.C.; Samy, W.; Chiu, C.H.; Gin, T. Effect of Hypovitaminosis D on Postoperative Pain Outcomes and Short-Term Health-Related Quality of Life After Knee Arthroplasty: A Cohort Study. Medicine 2015, 94, e1812. [Google Scholar] [CrossRef] [PubMed]
  34. Hajimohammadebrahim-Ketabforoush, M.; Shahmohammadi, M.; Khoundabi, B.; Shariatpanahi, Z.V. Effect of Vitamin D Supplementation on Postcraniotomy Pain After Brain Tumor Surgery: A Randomized Clinical Trial. World Neurosurg. 2019, 130, e105–e111. [Google Scholar] [CrossRef]
  35. Krasowska, K.; Skrobot, W.; Liedtke, E.; Sawicki, P.; Flis, D.J.; Dzik, K.P.; Libionka, W.; Kloc, W.; Kaczor, J.J. The preoperative supplementation with Vitamin D attenuated pain intensity and reduced the level of pro-inflammatory markers in patients after posterior lumbar interbody fusion. Front. Pharmacol. 2019, 10, 527. [Google Scholar] [CrossRef]
  36. Rastelli, A.L.; Taylor, M.E.; Gao, F.; Armamento-Villareal, R.; Jamalabadi-Majidi, S.; Napoli, N.; Ellis, M.J. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): A phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Res. Treat. 2011, 129, 107–116. [Google Scholar] [CrossRef]
  37. McCabe, P.S.; Pye, S.R.; Beth, J.M.; Lee, D.M.; Tajar, A.; Bartfai, G.; Boonen, S.; Bouillon, R.; Casanueva, F.; Finn, J.D.; et al. Low vitamin D and the risk of developing chronic widespread pain: Results from the European male ageing study. BMC Musculoskelet. Disord. 2016, 17, 32. [Google Scholar] [CrossRef]
  38. Chen, C.S.; Zirpoli, G.; Barlow, W.E.; Budd, G.T.; McKiver, B.; Pusztai, L.; Hortobagyi, G.N.; Albain, K.S.; Damaj, M.I.; Godwin, A.K.; et al. Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221. J. Natl. Compr. Cancer Netw. 2023, 21, 1172–1180. [Google Scholar] [CrossRef]
  39. Jennaro, T.S.; Fang, F.; Kidwell, K.M.; Smith, E.M.L.; Vangipuram, K.; Burness, M.L.; Griggs, J.J.; Van Poznak, C.; Hayes, D.F.; Henry, N.L.; et al. Vitamin D deficiency increases severity of paclitaxel-induced peripheral neuropathy. Breast Cancer Res. Treat. 2020, 180, 707–714. [Google Scholar] [CrossRef]
  40. Niravath, P.; Hilsenbeck, S.G.; Wang, T.; Jiralerspong, S.; Nangia, J.; Pavlick, A.; Ademuyiwa, F.; Frith, A.; Ma, C.; Park, H.; et al. Randomized controlled trial of high-dose versus standard-dose vitamin D3 for prevention of aromatase inhibitor-induced arthralgia. Breast Cancer Res. Treat. 2019, 177, 427–435. [Google Scholar] [CrossRef]
  41. Khan, Q.J.; Reddy, P.S.; Kimler, B.F.; Sharma, P.; Baxa, S.E.; O’Dea, A.P.; Klemp, J.R.; Fabian, C.J. Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Res. Treat. 2010, 119, 111–118. [Google Scholar] [CrossRef]
  42. Hao-Wei, X.; Shu-Bao, Z.; Yu-Yang, Y.; Chen, H.; Hu, T.; Shan-Jin, W. Relationship between vitamin D and nonspecific low back pain may be mediated by inflammatory markers. Pain Physician 2021, 24, E1015. [Google Scholar]
  43. Prieto-Alhambra, D.; Javaid, M.K.; Servitja, S.; Arden, N.K.; Martinez-García, M.; Diez-Perez, A.; Albanell, J.; Tusquets, I.; Nogues, X. Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: A prospective cohort study. Breast Cancer Res. Treat. 2011, 125, 869–878. [Google Scholar] [CrossRef]
  44. Chen, X.; Ji, Y.; Liu, R.; Zhu, X.; Wang, K.; Yang, X.; Liu, B.; Gao, Z.; Huang, Y.; Shen, Y.; et al. Mitochondrial dysfunction: Roles in skeletal muscle atrophy. J. Transl. Med. 2023, 21, 503. [Google Scholar] [CrossRef]
  45. Ersoy, S.; Kesiktas, F.N.; Sirin, B.; Bugdayci, D.; Paker, N. The effect of vitamin D treatment on quality of life in patients with fibromyalgia. Irish J. Med. Sci. 2024, 193, 1111–1116. [Google Scholar] [CrossRef]
  46. Simonetti, M.; Mauceri, D. Cellular and Molecular Mechanisms Underlying Pain Chronicity. Cells 2023, 12, 1126. [Google Scholar] [CrossRef]
  47. Pak, D.J.; Yong, R.J.; Kaye, A.D.; Urman, R.D. Chronification of Pain: Mechanisms, Current Understanding, and Clinical Implications. Curr. Pain Headache Rep. 2018, 22, 9. [Google Scholar] [CrossRef]
  48. Chapman, C.R.; Vierck, C.J. The Transition of Acute Postoperative Pain to Chronic Pain: An Integrative Overview of Research on Mechanisms. J. Pain 2017, 18, 359.e1–359.e38. [Google Scholar] [CrossRef]
  49. Epping-Jordan, J.E.; Wahlgren, D.R.; Williams, R.A.; Pruitt, S.D.; Slater, M.A.; Patterson, T.L.; Grant, I.; Webster, J.S.; Atkinson, J.H. Transition to chronic pain in men with low back pain: Predictive relationships among pain intensity, disability, and depressive symptoms. Health Psychol. 1998, 17, 421–427. [Google Scholar] [CrossRef]
  50. Gatchel, R.J.; Bevers, K.; Licciardone, J.C.; Su, J.; Du, Y.; Brotto, M. Transitioning from Acute to Chronic Pain: An Examination of Different Trajectories of Low-Back Pain. Healthcare 2018, 6, 48. [Google Scholar] [CrossRef]
  51. Neogi, T. The epidemiology and impact of pain in osteoarthritis. Osteoarthr. Cartil. 2013, 21, 1145–1153. [Google Scholar] [CrossRef]
  52. Zuqui-Ramírez, M.A.; Belalcazar-López, V.M.; Urenda-Quezada, A.; González-Rebatu y González, A.; Sander-Padilla, J.G.; Lugo-Sánchez, L.A.; Rodríguez-Vázquez, I.C.; Rios-Brito, K.F.; Arguedas-Núñez, M.M.; Canales-Vázquez, E. Multimodal Analgesia Approach in Acute Low Back Pain Management: A Phase III Study of a Novel Analgesic Combination of Etoricoxib/Tramadol. Pain Ther. 2024, 13, 1511–1528. [Google Scholar] [CrossRef] [PubMed]
  53. Shipton, E.A.; Shipton, E.E. Vitamin D and Pain: Vitamin D and Its Role in the Aetiology and Maintenance of Chronic Pain States and Associated Comorbidities. Pain Res. Treat. 2015, 2015, 904967. [Google Scholar] [CrossRef] [PubMed]
  54. Vieth, R.; Holick, M.F. Chapter 57B-The IOM—Endocrine Society Controversy on Recommended Vitamin D Targets: In Support of the Endocrine Society Position. In Vitamin D, 4th ed.; Feldman, D., Ed.; Academic Press: New York, NY, USA, 2018; pp. 1091–1107. ISBN 978-0-12-809965-0. [Google Scholar]
  55. Glare, P.; Aubrey, K.; Gulati, A.; Lee, Y.C.; Moryl, N.; Overton, S. Pharmacologic management of persistent pain in cancer survivors. Drugs 2022, 82, 275–291. [Google Scholar] [CrossRef]
  56. Soens, M.A.; Sesso, H.D.; Manson, J.E.; Fields, K.G.; Buring, J.E.; Lee, I.-M.; Cook, N.R.; Kim, E.; Bubes, V.; Dushkes, R.; et al. The effect of vitamin D and omega-3 fatty acid supplementation on pain prevalence and severity in older adults: A large-scale ancillary study of the VITamin D and OmegA-3 triaL (VITAL). Pain 2024, 165, 635–643. [Google Scholar] [CrossRef]
  57. Grant, W.B.; Wimalawansa, S.J.; Pludowski, P.; Cheng, R.Z. Vitamin D: Evidence-Based Health Benefits and Recommendations for Population Guidelines. Nutrients 2025, 17, 277. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Article Metrics

Citations

Article Access Statistics

Journal Statistics
Multiple requests from the same IP address are counted as one view.
Recent Research on the Role of Phytochemicals from Ginseng in Management of Osteosarcoma, Osteoporosis, and Osteoarthritis
Previous
Association of Coffee and Energy Drink Intake with Suicide Attempts and Suicide Ideation: A Systematic Review and Meta-Analysis
Next