Sex-Related Differences in Chronic Pain: A Narrative Review by a Multidisciplinary Task Force
Abstract
1. Introduction
- Summarize current evidence on sex-related differences in chronic pain epidemiology, mechanisms, and treatment response;
- Identify existing research gaps and barriers in clinical practice;
- Provide expert-driven suggestions for implementing more personalized and equitable approaches in chronic pain management.
2. Materials and Methods
3. Results and Discussion
3.1. Sex Differences in Chronic Pain: Prevalence, Perception, and Underlying Factors
3.2. Biological and Psycho-Social Factors Could Drive Sex Differences in Chronic Pain
3.2.1. Biological Factors
3.2.2. Psycho-Social Factors
3.3. Pharmacological Approaches to Chronic Pain Management
3.3.1. Sex Differences in Chronic Pain Treatment Response
3.3.2. Sex Differences in Adverse Drug Reactions and Pharmacokinetics in Chronic Pain Management
3.3.3. Psychological Interventions in Chronic Pain: Enhancing Quality of Life Through Tailored Therapies and a Multidisciplinary Approach
- Operant-behavioral therapy: Focuses on modifying behaviors that reinforce the pain experience [153].
- Cognitive behavioral therapy (CBT): Helps patients reframe negative thoughts about pain and develop coping strategies [154].
- Mindfulness-based stress reduction (MBSR): Uses mindfulness techniques to reduce stress and promote emotional well-being [155].
- Acceptance and commitment therapy (ACT): Encourages patients to accept pain and commit to living a meaningful life despite it [155].
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACT | Acceptance and commitment therapy |
AE | Adverse effect |
CBT | Cognitive behavioral therapy |
COMT | Catechol-O-methyltransferase |
CP | Chronic pain |
HPA | Hypothalamic–pituitary–adrenal |
IASP | International Association for the Study of Pain |
MBSR | Mindfulness-based stress reduction |
MOR | µ-opioid receptors |
NIH | National Institutes of Health |
NSAIDs | Non-steroidal anti-inflammatory drugs |
OPRM1 | Opioid receptor M 1 |
OXN | Oxycodone/naloxone |
PCA | Patient-controlled analgesia |
QoL | Quality of life |
SES | Socio-economic status |
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Domain | Section | Search Terms Used | Cited References * |
---|---|---|---|
Epidemiological | 3.1 | “chronic pain” AND (“sex differences” OR “gender differences”) AND (“hormones” OR “prevalence” OR “epidemiology” OR “treatment satisfaction” OR “coping” OR “comorbidity”) | [4,6,7,8,9,10,11,12,13,14,15,16,17,22,23,24,28,29,48,49,50,51,52,53,54,55,56] |
Biological mechanisms | 3.2.1 | “chronic pain” AND (“sex differences” OR “gender differences”) AND (“hormones” OR “hormonal fluctuations” OR “testosterone” OR “estrogen” OR “neuroimmune” OR “microglia” OR “T cells” OR “aging” OR “biomarkers”) | [15,16,17,28,29,30,31,32,33,49,50,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77] |
Psycho-social | 3.2.2 | “chronic pain” AND (“sex differences” OR “gender differences”) AND (“gender bias” OR “healthcare disparities” OR “social norms” OR “andronormativity” OR “cultural roles” OR “socio-economic status” OR “pain perception” OR “pain tolerance”OR “mental health” OR “depression” OR “anxiety” OR “coping strategies” OR “quality of life” OR “social support” OR “functioning” OR “pain acceptance”)) | [6,16,17,23,24,39,40,41,42,43,44,45,46,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113] |
Pharmacological strategies | 3.3.1 | “chronic pain” AND (“sex differences” OR “gender differences”) AND (“analgesics” OR “NSAIDs” OR “ibuprofen” OR “opioid efficacy” OR “treatment response” OR “pharmacokinetics” OR “pharmacodynamics” OR “adverse drug reactions” OR “pharmacokinetics” OR “pharmacodynamics” OR “opioid metabolism” OR “drug clearance” OR “reproductive health” OR “endocrine effects”) | [34,37,38,114,115,116,117,118,119,120,121,122,123,124,125,126,127] |
3.3.2 | “chronic pain” AND (“sex differences” OR “gender differences”) AND (“adverse drug reactions” OR “pharmacokinetics” OR “pharmacodynamics” OR “opioid metabolism” OR “drug clearance” OR “reproductive health” OR “endocrine effects”) | [39,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151] | |
3.3.3 | “chronic pain” AND (“psychological interventions” OR “psychotherapy” OR “cognitive behavioral therapy” OR “mindfulness-based stress reduction” OR “acceptance and commitment therapy” OR “quality of life” OR “coping strategies”) | [152,153,154,155,156] |
Key Domains in CP Management | Sex-Specific Considerations and Strategies |
---|---|
Biological and psycho-social interplay | Sex-related differences in CP stem from a complex interaction of biological and psycho-social factors. Effective management requires tailored, interdisciplinary strategies that address both dimensions. |
Pharmacological considerations | CP treatments, particularly opioids and NSAIDs, must account for sex-specific variations in drug response and adverse effects to optimize safety and efficacy. |
Psychological interventions | The integration of psychological strategies enhances CP management outcomes. These interventions should be personalized according to sex and individual coping mechanisms. |
Advancing precision medicine | Future approaches to pain management should prioritize gene therapy and the identification of sex-specific molecular targets to enhance precision and personalized treatment. |
Equity and policy implications | Achieving equitable pain care necessitates awareness of sex differences in CP, addressing translational gaps, incorporating psycho-social factors, and considering sex-specific pharmacokinetics and therapeutic targets. Clinicians and policymakers are urged to advocate for sex-aware guidelines and individualized care pathways. |
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© 2025 by the authors. Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Marchesini, M.; Fornasari, D.; Natoli, S.; Vegni, E.; Cuomo, A. Sex-Related Differences in Chronic Pain: A Narrative Review by a Multidisciplinary Task Force. Medicina 2025, 61, 1172. https://doi.org/10.3390/medicina61071172
Marchesini M, Fornasari D, Natoli S, Vegni E, Cuomo A. Sex-Related Differences in Chronic Pain: A Narrative Review by a Multidisciplinary Task Force. Medicina. 2025; 61(7):1172. https://doi.org/10.3390/medicina61071172
Chicago/Turabian StyleMarchesini, Maurizio, Diego Fornasari, Silvia Natoli, Elena Vegni, and Arturo Cuomo. 2025. "Sex-Related Differences in Chronic Pain: A Narrative Review by a Multidisciplinary Task Force" Medicina 61, no. 7: 1172. https://doi.org/10.3390/medicina61071172
APA StyleMarchesini, M., Fornasari, D., Natoli, S., Vegni, E., & Cuomo, A. (2025). Sex-Related Differences in Chronic Pain: A Narrative Review by a Multidisciplinary Task Force. Medicina, 61(7), 1172. https://doi.org/10.3390/medicina61071172