Search Results (28)

Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article

Orofacial pain (OFP) includes chronic pain conditions categorized into musculoskeletal (MS), neurovascular (NV), and neuropathic (NP) pain types, encompassing temporomandibular disorders (TMD), migraines, trigeminal neuralgia (TN), post-traumatic neuropathies, and burning mouth syndrome (BMS). These conditions significantly affect quality of life; yet, their underlying metabolic disruptions remain inadequately explored. Salivary metabolomics provides a non-invasive method to investigate biochemical alterations associated with OFP subtypes. This study aimed to identify pain-specific salivary metabolites across chronic OFP types and examine their correlations with clinical characteristics. Saliva samples from 63 OFP patients (TMD, migraines, TN, post-traumatic neuropathies, BMS) and 37 pain-free controls were analyzed using liquid chromatography–mass spectrometry (LC-MS) targeting 28 metabolites linked to pain. Statistical analyses determined significant metabolite changes and associations with pain subtypes and patient characteristics. Among the 28 analyzed metabolites, 18 showed significant differences between OFP patients and controls. Key amino acids, including DL-glutamic acid, DL-aspartic acid, DL-citrulline, spermidine, and DL-ornithine, were significantly elevated in MS, NV, and NP pain types compared to controls. Additionally, DL-glutamine, DL-valine, and DL-phenylalanine were distinctively elevated in TMD and migraine patients. BMS displayed fewer alterations, with significantly lower levels of DL-proline, DL-tryptophan, DL-glutamic acid, DL-asparagine, and DL-aspartic acid compared to other pain types but elevated spermidine levels relative to controls. Salivary metabolomics revealed distinct metabolic alterations in OFP subtypes, providing insights into potential biomarkers for diagnosis and monitoring. These findings offer a foundation for personalized approaches in OFP management, although further research is required to validate and expand these results. Full article

Post-traumatic trigeminal neuropathy (PTTN) is a sensory abnormality caused by injury to the trigeminal nerve during orofacial surgery. However, existing analgesics are ineffective against PTTN. Abnormal microglial activation in the caudal part of the spinal trigeminal nucleus caudal part (Sp5C), where the central trigeminal nerve terminals reside, plays an important role in PTTN pathogenesis. Therefore, regulating microglial activity in Sp5C appears to be an important approach to controlling pain in PTTN. Cannabinoid receptor 2 (CB₂) is expressed in immune cells including microglia, and its activation has anti-inflammatory effects. The current study demonstrates that the repeated intranasal administration of CB₂ agonist HU-308 ameliorates the infraorbital nerve cut (IONC)-induced hyperresponsiveness to acetone (cutaneous cooling). The therapeutic efficacy of oral HU-308 was found to be less pronounced in alleviating cold hypersensitivity in IONC mice compared to intranasal administration, indicating the potential advantages of the intranasal route. Furthermore, repeated intranasal administration of HU-308 suppressed the activation of Sp5C microglia in IONC mice. Additionally, pretreatment with the CB₂ antagonist, SR 144528, significantly blocked the anti-nociceptive effect of repeated intranasal administration of HU-308 on cold hypersensitization in IONC mice. These data suggest that the continuous stimulation of CB₂ ameliorates PTTN-induced pain via the inhibition of microglial activation. Thus, CB₂ agonists are potential candidates for novel therapeutic agents against PTTN. Full article

Background: Neuropathic pain results from a defect in the somatosensory nervous system caused by a diversity of etiologies. The effect of current treat-ment with analgesics and surgery is limited. Studies report the therapeutic use of adipose tissue-derived components to treat neuropathic pain as a new treatment modality. Objective: The aim of this systematic review was to investigate the therapeutic clinical efficacy of adipose tissue-derived components on neuro-pathic pain. Methods: PubMed, Medline, Cochrane and Embase databases were searched until August 2023. Clinical studies assessing neuropathic pain after autologous fat grafting or the therapeutic use of adipose tissue-derived com-ponents were included. The outcomes of interest were neuropathic pain and quality of life. Results: In total, 433 studies were identified, of which 109 dupli-cates were removed, 324 abstracts were screened and 314 articles were excluded. In total, ten studies were included for comparison. Fat grafting and cellular stromal vascular fraction were used as treatments. Fat grafting indications were post-mastectomy pain syndrome, neuromas, post-herpetic neuropathy, neuro-pathic scar pain and trigeminal neuropathic pain. In seven studies, neuropathic pain levels decreased, and overall, quality of life did not improve. Conclusions: The therapeutic efficacy of adipose tissue-derived components in the treatment of neuropathic pain remains unclear due to the few performed clinical trials with small sample sizes for various indications. Larger and properly designed (randomized) controlled trials are required. Full article

Painful traumatic trigeminal neuropathy (PTTN) is a chronic neuropathic pain that may develop following injury to the trigeminal nerve. Etiologies include cranio-orofacial trauma that may result from dental, surgical, or anesthetic procedures or physical trauma, such as a motor vehicle accident. Following nerve injury, there are various mechanisms, including peripheral and central, as well as phenotypic changes and genetic predispositions that may contribute to the development of neuropathic pain. In this article, we review current literature pertaining to the cellular processes that occur following traumatic damage to the trigeminal nerve, also called cranial nerve V, that results in chronic neuropathic pain. We examine the neurobiology and pathophysiology based mostly on pre-clinical animal models of neuropathic/trigeminal pain. Full article

Background: Postoperative trigeminal neuropathy may be seen after surgery for middle and posterior cranial fossa lesions. Although neuropathic pain is a cause of reduced quality of life, global consensus on postoperative pain management is lacking. Mirogabalin besylate is a selective ligand for the α2δ subunit of voltage-gated calcium channels. Although mirogabalin has been used for patients with postherpetic neuralgia and painful diabetic peripheral neuropathy, few reports have assessed the effect on postsurgical neuropathy. In this report, we describe a clinical effectiveness of mirogabalin for trigeminal neuropathy after skull base surgery. Case description: Case 1: A 51-year-old female with right trigeminal schwannoma was operated on via the anterior transpetrosal approach. She had tingling and numb feelings in the right face postoperatively. Mirogabalin was orally administered after the operation. Her continuous facial numbness immediately improved. Case 2: A 55-year-old female with left middle fossa base meningioma extending into the infratemporal fossa was operated on via the infratemporal fossa approach. She had a tingling feeling in the left face postoperatively. Mirogabalin was orally administered for this symptom after the operation, which gradually improved. Conclusions: Mirogabalin may show significant pain relief for patients with trigeminal neuropathy after skull base surgery. Further studies using a larger number of patients are warranted to confirm these findings. Full article

Painful post-traumatic trigeminal neuropathy (PTTN) is a known complication of dental implant therapy. Patients with PTTN develop sensory abnormalities in the orofacial region, which may be a psychosocial aspect, and dentists should assess somatosensory testing and psychosocial factors. The patients were assessed using quantitative sensory testing (QST). A 64-year-old female presented with allodynia of the left lower lip that occurred after a surgical implant procedure. Persistent pain started 4 months after the placement of two dental implants in the mandible. Sensory testing of these areas revealed warm hyposensitivity and mechanical hypersensitivity of the mandibular region. We also assessed PTTN-related perceived injustice using the Injustice Experience Questionnaire. The patient refused medication therapy such as pregabalin; therefore, autogenic training was adopted as an alternative management strategy. We conclude that for expensive dental procedures, such as implant placement, sufficient consensus should be obtained preoperatively before proceeding with surgery. Full article

Myelin-oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune-mediated demyelinating disease of the central nervous system (CNS). Patients with MOGAD may develop any combination of optic neuritis (ON), myelitis, brainstem syndrome and encephalitis. Reports of MOGAD with cranial nerve involvement are rare. Herein, we report a MOGAD patient with cranial neuropathies. In addition, we summarized the clinical features of the previously reported six MOG-IgG-positive cases with cranial nerve involvement and discussed the underlying mechanisms of MOGAD involving cranial nerves. Cranial neuropathy is an emerging phenotype in MOGAD, which has characteristics of both central and peripheral nervous system (PNS) involvement, with the trigeminal nerve being the most commonly affected nerve. MOG antibody testing in patients with cranial neuropathies is warranted, and immunotherapy is advocated when the risk of relapse is high. Although higher antibody titers and persistently positive serological test results are predictive of disease recurrence, the long-term outcomes of MOG-IgG-positive patients with cranial neuropathies remain largely unknown. Full article

Trigeminal neuralgia is a chronic pain condition associated with sharp, shock-like pain in one or more divisions of the trigeminal nerve. For patients who do not respond well to pharmacotherapy, there is growing evidence that Botulinum toxin type A injections into the trigeminal ganglion provide pain relief for several weeks up to several months at a time. One option is to administer injections into the trigeminal ganglion in Meckel’s cave by inserting a needle through the Pterygopalatine Fossa using fluoroscopy to guide and confirm the proper needle placement. However, there is evidence that Botulinum toxin travels across nerve synapses; thus, injecting directly into the trigeminal ganglion may not be necessary. We present two patients with a confirmed diagnosis of trigeminal neuralgia who were treated by injecting Botulinum toxin type A intraorally into the mental foramen which resulted in 6 months or longer of pain relief. Injections into the mental foramen are much easier to administer than those administered directly into the trigeminal ganglion, and both patients treated with this technique experienced comparable results to what can be expected from traditional fluoroscopy-guided botulinum toxin injections. Though more research is needed, these cases potentially imply that a less-invasive injection may be sufficient in managing trigeminal neuralgia-related pain. Full article

The endocannabinoid system is involved in physiological and pathological processes, including pain generation, modulation, and sensation. Its role in certain types of chronic orofacial pain (OFP) has not been thoroughly examined. By exploring the profiles of specific salivary endocannabinoids (eCBs) in individuals with different types of OFP, we evaluated their use as biomarkers and the influence of clinical parameters and pain characteristics on eCB levels. The salivary levels of anandamide (AEA), 2-arachidonoyl glycerol (2-AG), and their endogenous breakdown product arachidonic acid (AA), as well as the eCB-like molecules N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA), were assessed in 83 OFP patients and 43 pain-free controls using liquid chromatography/tandem mass spectrometry. Patients were grouped by diagnosis: post-traumatic neuropathy (PTN), trigeminal neuralgia (TN), temporomandibular disorder (TMD), migraine, tension-type headache (TTH), and burning mouth syndrome (BMS). Correlation analyses between a specific diagnosis, pain characteristics, and eCB levels were conducted. Significantly lower levels of 2-AG were found in the TN and TTH groups, while significantly lower PEA levels were found in the migraine group. BMS was the only group with elevated eCBs (AEA) versus the control. Significant correlations were found between levels of specific eCBs and gender, health-related quality of life (HRQoL), BMI, pain duration, and sleep awakenings. In conclusion, salivary samples exhibited signature eCBs profiles for major OFP disorders, especially migraine, TTH, TN, and BMS. This finding may pave the way for using salivary eCBs biomarkers for more accurate diagnoses and management of chronic OFP patients. Full article

Objective: The management of petroclival meningiomas (PCMs) remains notoriously difficult due to their close association with neurovascular structures and their complex anatomy, hence the surgical paradigm change from radical to functional resection in the past. With this study, we aimed to analyze surgical and functional outcomes of a modern consecutive series of patients with PCMs. Methods: We reviewed patient charts and imaging data of 64 consecutive patients from 2006 to 2018 with a PCM resected at our institution and compared surgical and functional outcomes between subgroups stratified by surgical approach. Results: Females comprised 67.2% of patients (n = 43), with a mean age of 55 years (median 56; range 21–84). Follow-up data were available for 68.8% and reached a mean of 42.3 months (range 1–129) with a median of 28.5 months. The mean tumor diameter was 37.3 mm (standard deviation (SD) 15.4; median 37.0). Infiltration of the cavernous sinus was observed in 34 cases (53.1%), and the lesions affected the brain stem in 28 cases (43.8%). Preoperative cranial nerve palsy was observed in 73.4% of cases; trigeminal neuropathy (42.2%), hearing loss (32.8%), and impairment of vision (18.8%) were the most common. A retrosigmoid approach was employed in 47 cases (78.1%), pterional in 10 (15.6%), combined petrosal in 2 (3.1%), and transnasal and subtemporal in 1 (1.6%). Fifteen cases (23.4%) were resected in a two-staged fashion. Gross total resection (GTR) was attempted in 30 (46.9%) cases without cavernous sinus infiltration and was achieved in 21 (70.0%) of these cases. Surgical complications occurred in 13 cases (20.3%), most commonly meningitis (n = 4; 6.3%). Postoperatively, 56 patients (87.5%) developed new cranial nerve palsy, of which 36 (63.6%) had improved or resolved on last follow up. Achieving GTR was not significantly associated with higher rates of surgical complications (chi-square; p = 0.288) or postoperative cranial nerve palsy (chi-square; p = 0.842). Of all cases, 20 (31.3%) underwent postoperative radiation. Tumor progression was observed in 10 patients (15.9%) after a mean 102 months (median 124). Conclusions: Surgical resection remains the mainstay of treatment for PCMs, with perioperative cranial neuropathies exhibiting favorable recovery rates. Most essentially, the preselection of patients with hallmarks of brain stem affection and cavernous sinus infiltration should dictate whether to strive for a functionally oriented strategy in favor of radical resection. Full article

Capsaicin is a chili peppers extract, genus Capsicum, commonly used as a food spice. Since ancient times, Capsaicin has been used as a “homeopathic remedy” for treating a wild range of pathological conditions but without any scientific knowledge about its action. Several studies have demonstrated its potentiality in cardiovascular, nephrological, nutritional, and other medical fields. Capsaicin exerts its actions thanks to the bond with transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is a nociceptive receptor, and its activation starts with a neurosensitive impulse, responsible for a burning pain sensation. However, constant local application of Capsaicin desensitized neuronal cells and leads to relief from neuropathic pain. In this review, we analyze the potential adjuvant role of Capsaicin in the treatment of different pathological conditions either in internal medicine or dentistry. Moreover, we present our experience in five patients affected by oro-facial pain consequent to post-traumatic trigeminal neuropathy, not responsive to any remedy, and successfully treated with topical application of Capsaicin. The topical application of Capsaicin is safe, effective, and quite tolerated by patients. For these reasons, in addition to the already-proven beneficial actions in the internal field, it represents a promising method for the treatment of neuropathic oral diseases. Full article

Background: Patients with Sjögren’s syndrome and polyneuropathy more frequently develop cranial nerve affection when compared to patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We therefore aimed to analyze trigeminal corneal nerve fibre characteristics in both patient groups. Methods: A total of 26 patients with Sjögren’s syndrome associated neuropathy and 29 patients with CIDP were recruited at our university hospital and compared to 6 healthy controls. Dry eye symptoms and signs were assessed via clinical examination and the Ocular Disease Surface Index questionnaire. Trigeminal corneal nerve fibres were analyzed via corneal confocal microscopy (CCM) as a non-invasive in vivo microscopy. Results: CCM revealed significantly reduced corneal nerve fibre density and corneal nerve fibre main branch density in the Neuro-Sjögren group when compared with healthy controls. There were no significant group differences between the Neuro-Sjögren and the CIDP group for any of the microscopic parameters. Dry eye assessment showed similarly reduced scores for both patient groups, while healthy controls showed better results for objective dry eye signs. There was no correlation between microscopic parameters of the corneal confocal microscopy and parameters of dry eye assessment. Conclusions: Our data revealed trigeminal corneal nerve affection in patients with neuropathy associated with Sjögren’s syndrome and patients with CIDP detected by CCM. No difference was found between both neuropathy groups indicating that CCM is not able to distinguish between both entities. Full article

Background: Persistent Idiopathic Facial Pain (PIFP), previously named Atypical Facial Pain (AFP) is a poorly understood condition, often diagnosed after several inconclusive investigations. The aim of this retrospective study was to evaluate the demographic and clinical characteristics of patients with PIFP referred to a Facial Pain Center. Methods: Between May 2011 and September 2014, data on 41 PIFP patients were analyzed regarding temporal, topographical and descriptive pain features, including onset, localization, pain descriptors and intensity. Pharmacological pain treatments were also registered. Finally, the presence and type of previous minor oro-surgery procedures in the painful area were investigated. Results: Demographic and clinical characterization were similar to PIFP patients reported in literature. The presence of previous minor oro-surgery procedures in the painful area was reported in most of these patients, in particular endodontic treatments and tooth extractions. Conclusions: This retrospective analysis showed a high prevalence of minor oro-surgery procedures in our population, while its role in PIFP pathophysiology remains unknown. A new classification of PIFP built around the main discriminant factor of presence of these procedures in the painful area could be considered while available data were still insufficient to define specific diagnostic criteria. Full article

The skin is a protective organ, able to decode a wide range of tactile, thermal, or noxious stimuli. Some of the sensors belonging to the transient receptor potential (TRP) family, for example, TRPV1, can elicit capsaicin-induced heat pain or histamine-induced itching sensations. The sensory nerve fibers, whose soma is located in the trigeminal or the dorsal root ganglia, are able to carry signals from the skin’s sensory receptors toward the brain via the spinal cord. In some cases, in response to environmental factors, nerve endings might be hyper activated, leading to a sensitive skin syndrome (SSS). SSS affects about 50% of the population and is correlated with small-fiber neuropathies resulting in neuropathic pain. Thus, for cosmetical and pharmaceutical industries developing SSS treatments, the selection of relevant and predictive in vitro models is essential. In this article, we reviewed the different in vitro models developed for the assessment of skin and neuron interactions. In a second part, we presented the advantages of microfluidic devices and organ-on-chip models, with a focus on the first model we developed in this context. Full article