Pain
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Chronic pain affects the life of millions of people. Current treatments have deleterious side effects. We have advanced a strategy for targeting protein interactions which regulate the N-type voltage-gated calcium (CaV2.2) channel as an alternative to direct channel block. ⋯ Using constellation pharmacology, a recently described high content phenotypic screening platform for functional fingerprinting of neurons that uses subtype-selective pharmacological agents to elucidate cell-specific combinations (constellations) of key signaling proteins that define specific cell types, we investigated if (S)-LCM preferentially acts on certain types of neurons. (S)-lacosamide decreased the dorsal root ganglion neurons responding to mustard oil, and increased the number of cells responding to menthol. Finally, (S)-LCM reversed thermal hypersensitivity and mechanical allodynia in a model of postoperative pain, and 2 models of neuropathic pain. Thus, using (S)-LCM to inhibit CRMP2 phosphorylation is a novel and efficient strategy to treat pain, which works by targeting specific sensory neuron populations.
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Pain biomarkers are warranted for individualized pain management. Based on different pain modulatory phenotypes, the objectives of this study were to explore the existence of subgroups within patients with nonmalignant chronic pain and to investigate differences in clinical pain and pain hypersensitivity between subgroups. Cuff algometry was performed on lower legs in 400 patients with chronic pain to assess pressure pain threshold, pressure pain tolerance, temporal summation of pain (TSP: increase in pain scores to 10 repeated stimulations), and conditioned pain modulation (CPM: increase in cuff pressure pain threshold during cuff pain conditioning on the contralateral leg). ⋯ Moreover, group 1 demonstrated higher clinical pain scores than group 4 (P < 0.05). Although not different between subgroups, patients were profiled on demographics, disability, pain catastrophizing, and fear of movement. Future research should investigate interventions tailored towards these subgroups.
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Sensitization of purinergic P2X3 receptors (P2X3Rs) is a major mechanism contributing to injury-induced exaggerated pain responses. We showed in a previous study that cyclic adenosine monophosphate (cAMP)-dependent guanine nucleotide exchange factor 1 (Epac1) in rat sensory dorsal root ganglia (DRGs) is upregulated after inflammatory injury, and it plays a critical role in P2X3R sensitization by activating protein kinase C epsilon (PKCε) inside the cells. protein kinase C epsilon has been established as the major PKC isoform mediating injury-induced hyperalgesic responses. On the other hand, the role of PKCα in receptor sensitization was seldom considered. ⋯ Because the application of Go6976 prior to CPT still reduces CPT-induced hyperalgesia, PKCα is downstream of Epacs to mediate the enhancement of P2X3R responses in DRGs. The pattern of translocation of PKCα inside DRG neurons in response to CPT or CFA stimulation is distinct from that of PKCε. Thus, in contrast to prevalent view, PKCα also plays an essential role in producing complex inflammation-induced receptor-mediated hyperalgesia.
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The McGill pain questionnaire (MPQ) and its later derivative the short form-MPQ have been used widely both in experimental and clinical pain studies. They have been of considerable importance in stimulating research into the perception of pain and now, with the publication of its latest variant, the short form-MPQ-2, it is appropriate to appraise their utility in the light of subsequent research into the nature of pain and the purpose of pain assessment. Following a description of the content and development of the questionnaires, issues of validity, reliability, and utility are addressed, not only in terms of the individual pain descriptors and the scales, but also in terms of methods of quantification. ⋯ It is suggested that pain assessment needs to be cast in its social context. We need to understand the influences on pain expression using a socio-communication model of pain that recognizes the function of pain and the importance of both innate pain responses and the effects of social learning. The review concludes with recommendations for future use of the MPQ and identifies a number of research challenges which lie ahead.
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Observational Study
The Heterogeneity Of Headache Patients Who Self-Medicate: A Cluster Analysis Approach.
Patients with headache often self-treat their condition with over-the-counter analgesics. However, overuse of analgesics can cause medication-overuse headache. The present study aimed to identify subgroups of individuals with headache who self-medicate, as this could be helpful to tailor intervention strategies for prevention of medication-overuse headache. ⋯ Cluster 3 (n = 222, 21.7%) mostly consisted of patients with migraine who also report pain in many other locations. These patients reported a high disability and a severe limitation of activities. They also showed the highest rates of MO (73%).