TRPA1 analgesia is mediated by kappa opioid receptors
Semizoglou, E.; Gentry, C.; Vastani, N.; Stucky, C. L.; Andersson, D. A.; Bevan, S.
Show abstract
TRPA1 expressed in peripheral sensory neurons is important for nociception. Pharmacological inhibition or genetic ablation of TRPA1 profoundly reduces normal behavioural sensitivity to noxious cold and mechanical stimulation, as well as sensory neuron responses to mechanical stimulation. TRPA1 inhibition also reverses cold and mechanical hypersensitivities in chronic pain models in vivo. Here we demonstrate that these striking effects of TRPA1 inactivation result from an increased constitutive activity of kappa opioid receptors (KOR) co-expressed with TRPA1 in sensory neurons. Inhibition of KOR in Trpa1-/- mice restores nociception and neuronal activity to the levels observed in wild-type mice and reverses the analgesic effects of TRPA1 antagonism in naive mice and in neuropathic and inflammatory pain conditions. TRPA1 regulation of KOR activity in sensory neurons provides a novel mechanism to produce peripherally mediated analgesia. Our findings suggest that TRP channel regulation of constitutive GPCR activity, may be a process of general physiological importance.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Endogenous inflammatory mediators produced by injury activate TRPV1 and TRPA1 nociceptors to induce sexually dimorphic cold pain that is dependent on TRPM8 and GFRalpha3 97%
- Parabrachial nucleus activity in nociception and pain in awake mice 96%
- C-Jun N-terminal kinase post-translational regulation of pain-related Acid-Sensing Ion Channels 1b and 3 96%
Similar papers in this journal
- Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats 97%
- Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain 97%
- Pruriception and neuronal coding in nociceptor subtypes in human and nonhuman primates 97%
Similar papers in this journal
- Studies on CRMP2 SUMOylation-deficient transgenic mice identify sex-specific NaV1.7 regulation in the pathogenesis of chronic neuropathic pain 96%
- Examination of the contribution of Nav1.7 to axonal propagation in nociceptors 95%
- Bradykinin receptor expression and bradykinin-mediated sensitization of human sensory neurons 95%
Similar papers in this journal
- Sensitisation of colonic nociceptors by TNFα is dependent on TNFR1 expression and p38 MAPK activity 96%
- Morphine-induced mechanical hypersensitivity in mice requires delta receptors, beta-arrestin2 and c-Src activity 96%
- Junctophilin-4 is essential for signalling at plasma membrane-endoplasmic reticulum junctions in sensory neurons 95%
Similar papers in this journal
- A role for protease activated receptor type 3 (PAR3) in nociception demonstrated through development of a novel peptide agonist 98%
- Mouse models of non-dystrophic and dystrophic myotonia exhibit nociplastic pain-like behaviors 98%
- De novo expression of neuropeptide Y in sensory neurons does not contribute to peripheral neuropathic pain 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.