Potamotrygon motoro stingray venom induces both neurogenic and inflammatory pain behavior in rodents

Toxicon. 2018 Aug:150:168-174. doi: 10.1016/j.toxicon.2018.05.018. Epub 2018 May 25.

Abstract

Freshwater stingray accidents cause an immediate, intense, and unrelieved pain which is followed by edema, erythema and necrosis formation. Treatment for stingray envenomation is based on administration of analgesic, antipyretic and anti-inflammatory drugs. Concerning pain control, it is prescribed to immerse punctured limb on hot water to alleviate pain. There are no studies demonstrating specific targets on which stingray venom acts to promote pain. Therefore, the aim of this work was to investigate some mechanisms of Potamotrygon motoro venom (PmV) that contribute to nociception induction. Evaluating spontaneous pain behavior in mice injected i.pl. with PmV, it was seen that PmV induced both neurogenic and inflammatory pain. PmV also induced hyperalgesia in both mice and rats, evaluated through electronic von Frey and rat paw pressure test, respectively. Partial inhibition of hyperalgesia was observed in mice treated with cromolyn or promethazine, which indicated that mast cell and histamine via H1 receptor participate in the inflammatory pain. To search for some targets involved in PmVinduced hyperalgesia, the participation of TRPV1, calcium channels, neurokinins, CGRP, and norepinephrine, was evaluated in rats. It was seen that PmV-induced hyperalgesia occurs with the participation of neurokinins, mainly via NK1 receptor, CGRP, and calcium influx, through both P/Q and L-type voltage-dependent calcium channels, besides TRPV1 activation. The data presented herein indicate that PmV causes hyperalgesia in rodents which is dependent on the participation of several neuroinflammatory mediators.

Keywords: Inflammatory pain; Neurogenic pain; Pain mediators; Potamotrygon motoro; Stingray venom.

MeSH terms

  • Animals
  • Behavior, Animal
  • Calcitonin Gene-Related Peptide
  • Fish Venoms / chemistry*
  • Histamine / metabolism
  • Hyperalgesia / chemically induced
  • Inflammation / chemically induced*
  • Male
  • Mast Cells
  • Mice
  • Pain / chemically induced*
  • Pain Measurement*
  • Rats
  • Rats, Wistar
  • Receptors, Histamine H1
  • Skates, Fish
  • Tachykinins

Substances

  • Fish Venoms
  • Receptors, Histamine H1
  • Tachykinins
  • Histamine
  • Calcitonin Gene-Related Peptide