Antiallodynic effect of intrathecal resiniferatoxin on neuropathic pain model of chronic constriction injury

Abstract

Injuries and/or dysfunctions in the somatosensory system can lead to neuropathic pain. Transient receptor potential vanilloid sub‑type 1 (TRPV1) play an important role in the development of allodynia and hyperalgesia following injury and the ensuing inflammatory conditions. Resiniferatoxin (RTX) is an ultrapotent synthetic TRPV1 agonist and many different administration routes are available for different mechanisms and different effects. RTX is used intraperitonially as amodel of neuropathic pain or epidurally and topically to produce prolonged analgesic effects. However, the use of RTX is controversial because its neurotoxicity and margin of safety have not been addressed adequately. The present study evaluates the effect of intrathecal RTX on the induction and allodynia behavior of animals submitted to neuropathic pain by chronic constriction injury (CCI). 160 Swiss mice were randomly distributed into two groups: intrathecal pre‑treatment group (PRE) aiming the effect in induction of allodynia and late intrathecal treatment group (POST) to evaluate the antiallodynic effect of the RTX on mechanical nociceptive threshold evaluated by the Von Frey hair filaments. Additionally, we evaluated the expression of TRPV1 in dorsal root ganglia (DRG) by western blotting after PRE‑ and POST‑treatment with RTX. Our results showed that the CCI mice developed prolonged mechanical allodynia‑like behavior in ipsilateral paw after surgery up to 24hours. The PRE‑ and POST‑treatment groups presented significant antiallodynic effects in ipsilateral paw for 24hours. Only the POST‑treatment group showed asignificant reduction of expression of the TRPV1 receptor after CCI. The presented data demonstrated that both PRE‑ and POST‑treatment with RTX given intrathecally produced potent antiallodynic activities in CCI mice and that POST‑treatment can reduce TRPV1 expression in DRG, suggesting that POST‑treatment RTX can revert central sensitization and its associated allodynia.