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.

• Authors: Veronica Cernit, Jacques Sénécal, Rahmeh Othman, Réjean Couture
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 3 (Jan 27 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32012798 (Publication Type: Journal Article)

Chemical References

• Bradykinin B1 Receptor Antagonists
• RNA, Messenger
• Receptor, Bradykinin B1
• TRPV Cation Channels
• Trpv1 protein, rat

Topics

• Animals
• Astrocytes (metabolism)
• Bradykinin B1 Receptor Antagonists (pharmacology)
• Disease Models, Animal
• Ganglia, Spinal (metabolism)
• Neuralgia (etiology, metabolism, physiopathology)
• Nociceptive Pain
• RNA, Messenger (genetics, metabolism)
• Rats
• Receptor, Bradykinin B1 (metabolism)
• Spinal Cord (metabolism)
• TRPV Cation Channels (metabolism)