Using the complete Freund's adjuvant (CFA) inflammatory pain model to examine the role of TRPV1 in regulating endogenous opioid analgesia in mice, we found that naloxone methiodide (Nal-M), a peripherally restricted, nonselective, and competitive opioid receptor antagonist, slowed the recovery from CFA-induced hypersensitivity in wild-type, but not TRPV1-deficient, mice.
These results suggest that PKC-mediated phosphorylation of TRPV1 S801 contributes to inflammation-mediated sensitization of TRPV1 to ligand, but not heat, <i>in vivo</i> Further, this suggests that interference with TRPV1 S801 phosphorylation might represent one potential way to attenuate inflammatory pain, yet spare basal sensitivity and produce fewer side effects than more general TRPV1 inhibition.<b>SIGNIFICANCE STATEMENT</b> Transient receptor potential vanilloid subtype 1 (TRPV1) has been considered a potential target for pain intervention.
Herein, complete Freund's adjuvant (CFA)-induced inflammatory pain model in rats and in-vitro calcium imaging studies were used to evaluate the mechanisms that underlie the antinociceptive effects of PEA, including modulating the activity of the transient receptor potential vanilloid receptor 1, which is a key receptor involved in the development of inflammatory pain.
In this study, we determined the contribution of presynaptic TRPA1 and TRPV1 at the spinal cord level to regulating nociceptive drive in chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in rats.
This study aimed to investigate the involvement of MrgprC and its transient receptor potential vanilloid 1 (TRPV1) pathway in EA analgesia in chronic inflammatory pain.
Importantly, intrathecal administration of the transmembrane peptide transactivator of transcription (TAT)-31-50 remarkably reduces Ca<sup>2+</sup> influx via TRPV1 in DRG neurons and alleviates thermal hyperalgesia and gait alterations in a complete Freund's adjuvant-induced inflammatory pain model in male rats.
Transient receptor potential vanilloid 1 (TRPV1) is known to be involved in acute to subacute neuropathic and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are not elucidated.
One key pathway that has been shown to be involved in inflammatory pain is Gq/GPCR, whose activation by inflammatory mediators is followed by the regulated response of the cation channel transient receptor potential vanilloid 1 (TRPV1).
These results suggest that the involvement of TRPV1 in TNF-induced pain offers new TRPV1-based experimental therapeutic approaches and demonstrates the analgesic potential of RTX in inflammatory pain diseases.
The transient receptor potential vanilloid type 1 (TRPV1) receptor is a polymodal molecular integrator in the pain pathway expressed in Aδ- and C-fibre nociceptors and is responsible for the thermal hyperalgesia associated with inflammatory pain.
Notably, intrathecal administration of the interfering peptide against the phosphorylation of Thr-406 alleviated heat hyperalgesia and reduced the surface level of TRPV1 in inflammatory pain rats.
TRPV1 is both activated and sensitized by inflammatory endogenous mediators during inflammatory pain conditions and appears to be up regulated in neuropathic pain conditions.
Indeed, a number of small-molecule TRPV1 antagonists are already undergoing Phase I/II clinical trials for the indications of chronic inflammatory pain and migraine.