Reciprocal Regulatory Interaction between TRPV1 and Kinin B1 Receptor in a Rat Neuropathic Pain Model

Abstract

Kinins are mediators of pain and inflammation and evidence suggests that the inducible kinin B1 receptor (B1R) is involved in neuropathic pain (NP). This study investigates whether B1R and TRPV1 are colocalized on nociceptors and/or astrocytes to enable regulatory interaction either directly or through the cytokine pathway (IL-1β, TNF-α) in NP. Sprague Dawley rats were subjected to unilateral partial sciatic nerve ligation (PSNL) and treated from 14 to 21 days post-PSNL with antagonists of B1R (SSR240612, 10 mg·kg−1, i.p.) or TRPV1 (SB366791, 1 mg·kg−1, i.p.). The impact of these treatments was assessed on nociceptive behavior and mRNA expression of B1R, TRPV1, TNF-α, and IL-1β. Localization on primary sensory fibers, astrocytes, and microglia was determined by immunofluorescence in the lumbar spinal cord and dorsal root ganglion (DRG). Both antagonists suppressed PSNL-induced thermal hyperalgesia, but only SB366791 blunted mechanical and cold allodynia. SSR240612 reversed PSNL-induced enhanced protein and mRNA expression of B1R and TRPV1 mRNA levels in spinal cord while SB366791 further increased B1R mRNA/protein expression. B1R and TRPV1 were found in non-peptide sensory fibers and astrocytes, and colocalized in the spinal dorsal horn and DRG, notably with IL-1β on astrocytes. IL-1β mRNA further increased under B1R or TRPV1 antagonism. Data suggest that B1R and TRPV1 contribute to thermal hyperalgesia and play a distinctive role in allodynia associated with NP. Close interaction and reciprocal regulatory mechanism are suggested between B1R and TRPV1 on astrocytes and nociceptors in NP.

Betaine Attenuates Chronic Constriction Injury-Induced Neuropathic Pain in Rats by Inhibiting KIF17-Mediated Nociception

“…The TRPV1 channel mediated sensitization and upregulation of protein expression during the development of neuropathic pain. − Transient receptor potential vanilloid channel 1 (TRPV1) is of critical importance in the generation and maintenance of neuropathic pain. TRPV1 is predominantly expressed on peripheral nociceptors.…”

Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice

“…Moreover, blockade of ACE prevents the formation of Ang II but also avoid the degradation of kinins and downregulates the bradykinin B1 receptor ( Estrela et al, 2020 ). B1 receptor is upregulated during neuroinflammation and is involved in neuropathic pain ( Ferreira et al, 2005 ; Cernit et al, 2020 ). Thus, downregulation of B1 receptor could be involved in the beneficial effect of ramipril.…”

JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice

“…Several studies have related the suppression of spinal astrocytes activation to the analgesia of oxaliplatin-induced neuropathic pain [20,22,29,45]. Although the mechanism by which astrocytes are activated in pain conditions remains to be elucidated, a close relationship between spinal TRPV1 and astrocytes in pain development has been reported [14], as the activity of both increased in various animal models of pain [17,54,55]. In the CFA model, the administration of diacerein, which has anti-arthritic properties, lowered inflammatory pain behavior and alleviated the upregulation of spinal TRPV1 and astrocytes [53].…”