Orofacial Pain: Molecular Mechanisms, Diagnosis, and Treatment 2021.

The Special Issue "Orofacial Pain: Molecular Mechanisms, Diagnosis, and Treatment 2021" contains 6 articles published by 41 authors from different countries focusing on nucleus accumbens core GABAergic neurons, receptor-interacting serine/threonine-protein kinase 1, pannexin 1-mediated ATP signaling, ultra-low-frequency transcutaneous electrical nerve stimulation, and triamcinolone acetonide. The content covers several pain models, including neuropathic pain caused by peripheral nerve constriction or malpositioned dental implants, tongue cancer, myogenous temporomandibular dysfunction, and oral ulcerative mucositis. In addition, a review paper on trigeminal neuralgia is included.

A psychophysical study comparing massage to conditioned pain modulation: A single blind randomized controlled trial in healthy participants.

INTRODUCTION: Pain-inducing massage results in greater pain inhibition than pain free massage, suggesting a mechanism dependent on conditioned pain modulation (CPM). The purpose of this study was to test the hypothesis that pain inducing massage produces similar magnitude of reduction in pain sensitivity as a cold pressor task and that baseline conditioned pain modulation efficiency predicts pain inducing massage related hypoalgesia. METHODS: Sixty healthy participants were randomly assigned to receive either pain inducing massage to the neck, cold pressor task to the hand, or pain free massage to the neck. Participants also underwent pre and immediate post-intervention quantitative sensory testing. A repeated measures ANCOVA determined between group differences in pain sensitivity changes. RESULTS: Pain inducing massage used as a conditioning stimulus resulted in comparable experimental pain sensitivity changes as a cold pressor task (p > 0.05). Pain intensity during the intervention demonstrated a weak correlation (r = 0.20, p = 0.12) with changes in pain sensitivity at a remote site. Individuals with an efficient CPM at baseline who received the pain inducing massage displayed greater increases in pressure pain threshold compared to individuals with a less efficient CPM indicating the potential benefit of treatment stratification by mechanism. CONCLUSION: Although pain inducing massage resulted in less self-reported pain than a cold pressor task, both resulted in similar magnitude of the CPM response, suggesting shared underlying mechanisms. Understanding mechanisms of interventions can move us closer to mechanistic based treatments for pain which is consistent with a personalized medicine approach to care.

Phytochemical screening of aqueous leaf extract of Blighia sapida K.D. Koenig (Sapindaceae) and its analgesic property in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Blighia sapida is traditionally used in treating intercostal pain, psychosis, stomach ache, back pain, and skin diseases. However, there is limited information on the scientific basis for its use traditionally in the treatment of pain. AIM OF STUDY: To identify the major constituents in the aqueous leaf extract of Blighia sapida (AEBS) and to assess its analgesic properties in mice. MATERIALS AND METHODS: Bioactive compounds were identified and quantified in AEBS by High Performance Liquid Chromatography/Photodiode Array Detector (HPLC/DAD). Analgesic activity of AEBS was assessed at doses of 125, 250, and 500 mg/kg p.o., using animal models. RESULTS: Chlorogenic acid, saponins, tannins, caffeic acid, quercetin, gallic acid, pyrogallol, quinine, caffeine, and nicotine were identified. At doses 250 mg/kg (p < 0.05) and 500 mg/kg (p < 0.01), AEBS significantly inhibited acetic acid induced writhing in comparison with the control. It also significantly inhibited pain in the inflammatory phase of the formalin induced paw licking test at 250 mg/kg (p < 0.01) and 500 mg/kg (p < 0.05) doses, in comparison with the control. It did not inhibit pain in the neurogenic phase of the formalin paw licking and in the hot plate tests. CONCLUSION: Blighia sapida leaf extract possesses analgesic activity that is mediated by peripheral mechanisms but not through central mechanisms.

Potential Nervous System Sensitization in Patients With Persistent Lower Extremity Tendinopathies: 3 Case Reports.

BACKGROUND: Tendinopathy is a condition often associated with pain and functional and sport performance limitations. While targeted exercise prescriptions are often effective, many patients with tendinopathy develop persistent symptoms. Emerging evidence suggests a possible link between nervous system sensitization and tendinopathy. If so, identifying and treating specific pain mechanisms may improve outcomes. CASE DESCRIPTION: Three patients were seen in physical therapy for complaints of ongoing chronic tendon pain and self-reported disability, despite being treated previously and receiving evidence-informed care. Upon examination, each patient demonstrated signs consistent with possible dysfunction of central pain mechanisms. Joint mobilization, pain neuroscience education, and aerobic exercise were primary interventions in each case to decrease pain and improve function. OUTCOMES: The 3 patients were treated for 5 sessions over the course of 8 weeks. Clinically significant improvement was noted in measures of pain, self-reported function, and pressure pain thresholds. At discharge, all patients were able to run without symptoms, and improvement was maintained at 1-year follow-up. DISCUSSION: Tendinopathy, while often described as local pain and dysfunction, may be associated with dysfunction of the nervous system. Identifying and treating pain mechanisms in addition to relevant impairments may be an appropriate intervention approach for individuals with tendinopathy. LEVEL OF EVIDENCE: Therapy, level 4. J Orthop Sports Phys Ther 2019;49(4):272-279. Epub 13 Feb 2019. doi:10.2519/jospt.2019.8600.

A Mechanism-Based Approach to the Management of Osteoarthritis Pain.

Pain from osteoarthritis (OA) affects millions of people worldwide, yet treatments are limited to acetaminophen, NSAIDs, physical therapy, and ultimately, surgery when there is significant disability. In recent years, our understanding of pain pathways in OA has developed considerably. Though joint damage and inflammation play a significant role in pain generation, it is now understood that both central and peripheral nervous system mechanisms exacerbate symptoms. Evolving management strategies for OA address central factors (e.g., sleep difficulties, catastrophizing, and depression) with treatments such as cognitive behavioral therapy and exercise. In addition, emerging data suggest that antibodies against peripheral signaling neuropeptides, such as nerve growth factor-1 (NGF-1), may significantly alleviate pain. However, concerns regarding potential adverse effects, such as rapidly progressive OA, still remain. A nuanced understanding is essential if we are to make headway in developing more effective treatments for OA.

Recent advances in postoperative pain management.

Good pain control after surgery is important to prevent negative outcomes such as tachycardia, hypertension, myocardial ischemia, decrease in alveolar ventilation, and poor wound healing. Exacerbations of acute pain can lead to neural sensitization and release of mediators both peripherally and centrally. Clinical wind up occurs from the processes of N-Methyl D-Aspartate (NMDA) activation, wind up central sensitization, long-term potentiation of pain (LTP), and transcription-dependent sensitization. Advances in the knowledge of molecular mechanisms have led to the development of multimodal analgesia and new pharmaceutical products to treat postoperative pain. The new pharmacological products to treat postoperative pain include extended-release epidural morphine and analgesic adjuvants such as capsaicin, ketamine, gabapentin, pregabalin dexmetomidine, and tapentadol. Newer postoperative patient-controlled analgesia (PCA) in modes such as intranasal, regional, transdermal, and pulmonary presents another interesting avenue of development.