capsazepine and Chronic-Pain

Topics: Analgesics; Animals; Chronic Pain; Fabaceae; Facial Pain; Lectins; Nociception; Rats; Rodentia; TRPV Cation Channels; Zebrafish; Zebrafish Proteins

Low-level laser therapy (LLLT) is widely used in pain control in the field of physical medicine and rehabilitation and is effective for fibromyalgia pain. However, its analgesic mechanism remains unknown. A possible mechanism for the effect of LLLT on fibromyalgia pain is via the antinociceptive signaling of substance P in muscle nociceptors, although the neuropeptide has been known as a neurotransmitter to facilitate pain signals in the spinal cord.. To establish an animal model of LLLT in chronic muscle pain and to determine the role of substance P in LLLT analgesia.. We employed the acid-induced chronic muscle pain model, a fibromyalgia model proposed and developed by Sluka et al., and determined the optimal LLLT dosage.. LLLT with 685 nm at 8 J/cm2 was effective to reduce mechanical hyperalgesia in the chronic muscle pain model. The analgesic effect was abolished by pretreatment of NK1 receptor antagonist RP-67580. Likewise, LLLT showed no analgesic effect on Tac1-/- mice, in which the gene encoding substance P was deleted. Besides, pretreatment with the TRPV1 receptor antagonist capsazepine, but not the ASIC3 antagonist APETx2, blocked the LLLT analgesic effect.. LLLT analgesia is mediated by the antinociceptive signaling of intramuscular substance P and is associated with TRPV1 activation in a mouse model of fibromyalgia or chronic muscle pain. The study results could provide new insight regarding the effect of LLLT in other types of chronic pain.

Topics: Acids; Animals; Capsaicin; Chronic Pain; Cnidarian Venoms; Disease Models, Animal; Dose-Response Relationship, Drug; Fibromyalgia; Laser Therapy; Low-Level Light Therapy; Mice; Mice, Inbred C57BL; Mice, Knockout; Musculoskeletal Pain; Protein Precursors; Signal Transduction; Substance P; Tachykinins; TRPV Cation Channels

The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas capsazepine treatment of mice at two weeks following SΦ874 infection did not reduce chronic allodynia. TRPV1-deficient mice did not develop chronic allodynia either. Similar results were found using novelty-suppressed feeding (NSF) to assess depressive behavior associated with neuropathic pain. Imaging of reporter mice also revealed induction of MCP-1 and CCR2 expression in sacral dorsal root ganglia following SΦ874 infection. Treatment with a CCR2 receptor antagonist at two weeks post-infection reduced chronic allodynia. Taken together, these results suggest that TRPV1 has a role in the establishment of post-UTI chronic pain, and CCR2 has a role in maintenance of post-UTI chronic pain.

Topics: Animals; Capsaicin; Chemokine CCL2; Chronic Pain; Disease Models, Animal; Female; Ganglia, Spinal; Gene Expression Regulation; Hyperalgesia; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Pelvic Pain; Receptors, CCR2; Signal Transduction; Toll-Like Receptor 4; TRPV Cation Channels; Urinary Tract Infections; Uropathogenic Escherichia coli

Substance P is an important neuropeptide released from nociceptors to mediate pain signals. We recently revealed antinociceptive signaling by substance P in acid-sensing ion channel 3 (ASIC3)-expressing muscle nociceptors in a mouse model of acid-induced chronic widespread pain. However, methods to specifically trigger the substance P antinociception were still lacking.. Here we show that acid could induce antinociceptive signaling via substance P release in muscle. We prevented the intramuscular acid-induced hyperalgesia by pharmacological inhibition of ASIC3 and transient receptor potential V1 (TRPV1). The antinociceptive effect of non-ASIC3, non-TRPV1 acid signaling lasted for 2 days. The non-ASIC3, non-TRPV1 acid antinociception was largely abolished in mice lacking substance P. Moreover, pretreatment with substance P in muscle mimicked the acid antinociceptive effect and prevented the hyperalgesia induced by next-day acid injection.. Acid could mediate a prolonged antinociceptive signaling via the release of substance P from muscle afferent neurons in a non-ASIC3, non-TRPV1 manner.

Topics: Acid Sensing Ion Channels; Acids; Animals; Capsaicin; Chronic Pain; Cnidarian Venoms; Disease Models, Animal; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Pain Measurement; Signal Transduction; Substance P; TRPV Cation Channels