The journal of pain : official journal of the American Pain Society
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Resolvin D5 (RvD5) is a specialized pro-resolving lipid mediator with potent anti-inflammatory and analgesic properties. Orofacial pain conditions, especially those that are chronic, present clinical challenges in terms of pharmacological management. Thus, new therapeutic options are clearly warranted. ⋯ This article presents a translational potential of RvD5 for targeted therapies aiming at the control of acute and chronic trigeminal pain, but further studies are needed to elucidate its sex-related mechanisms. PERSPECTIVE: This study demonstrated that RvD5 may provide the benefits for trigeminal neuropathic pain treatment in male and female rats, but its effect on inflammatory orofacial pain seems to be restricted only to males. Also, it provided the evidence for sex dichotomy in the mechanisms related to the antinociceptive effect of RvD5.
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Integrated pain management (IPM) programs can help to reduce the substantial population health burden of musculoskeletal pain, but are poorly implemented. Lessons learned from existing programs can inform efforts to expand IPM implementation. This qualitative study describes how health care systems, payers, providers, health policy researchers, and other stakeholders are overcoming barriers to developing and sustaining IPM programs in real-world settings. ⋯ Lessons from existing programs provide direction on to grow and support such IPM delivery models across a variety of settings. PERSPECTIVE: Integrated pain management (IPM) programs face numerous implementation challenges related to payment, organizational change, care coordination, and regulatory requirements. Drawing on real-world experiences of existing programs and from diverse IPM stakeholders, we outline actionable strategies that health care systems, providers, and payers can use to expand implementation of these programs.
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The method-of-limits (MLI) is an established psychophysical procedure, for example for determining thermal thresholds. The standard MLI relies on fixating the thermode at the stimulation site by means of a strap and requires the participant to terminate the increase in heat by pressing a button. This, however, raises concerns regarding safety and task complexity in specific populations, such as cognitively impaired individuals, people with high fear of pain or young children (< 6 years). ⋯ For none of the outcomes significant differences between the 2 methods were found. PERSPECTIVE: In the present study in healthy adults, an adapted simplified and safe method of limits was demonstrated to be equivalent to the standard method-of-limits. This novel behavioral "hand-withdrawal-method" seems promising for future investigations of pain sensitivity and placebo effects, especially for specific populations such as young children.
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Temporomandibular disorder (TMD) pain that involves inflammation and injury in the temporomandibular joint (TMJ) and/or masticatory muscle is the most common form of orofacial pain. We recently found that transient receptor potential vanilloid-4 (TRPV4) in trigeminal ganglion (TG) neurons is upregulated after TMJ inflammation, and TRPV4 coexpresses with calcitonin gene-related peptide (CGRP) in TMJ-innervating TG neurons. Here, we extended these findings to determine the specific contribution of TRPV4 in TG neurons to TMD pain, and examine whether sensory neuron-TRPV4 modulates TMD pain via CGRP. ⋯ These results suggest that TRPV4 in TG neurons contributes to TMD pain by potentiating CGRP secretion. PERSPECTIVE: This study demonstrates that activation of TRPV4 in TG sensory neurons drives pain by potentiating the release of pain mediator CGRP in mouse models of TMJ inflammation and masseter muscle injury. Targeting TRPV4 and CGRP may be of clinical potential in alleviating TMD pain.
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Administration of cisplatin and other chemotherapy drugs is crucial for treating tumors. However, cisplatin-induced pain hypersensitivity is still a critical clinical issue, and the underlying molecular mechanisms have remained unresolved to date. In this study, we found that repeated cisplatin treatments remarkedly upregulated the P2Y12 expression in the spinal cord. ⋯ Collectively, our data suggest that microglia P2Y12-SFK-p38 signaling contributes to cisplatin-induced pain hypersensitivity via IL-18-mediated central sensitization in the spinal, and P2Y12 could be a potential target for intervention to prevent chemotherapy-induced pain hypersensitivity. PERSPECTIVE: Our work identified that P2Y12/IL-18 played a critical role in cisplatin-induced pain hypersensitivity. This work suggests that P2Y12/IL-18 signaling may be a useful strategy for the treatment of chemotherapy-induced pain hypersensitivity.