Mechanisms involved in antinociception induced by a polysulfated fraction from seaweed Gracilaria cornea in the temporomandibular joint of rats

Int J Biol Macromol. 2017 Apr:97:76-84. doi: 10.1016/j.ijbiomac.2017.01.017. Epub 2017 Jan 5.

Abstract

Temporomandibular disorder is a common clinical condition involving pain in the temporomandibular joint (TMJ) region. This study assessed the antinociceptive effects of a polysulfated fraction from the red seaweed Gracilaria cornea (Gc-FI) on the formalin-induced TMJ hypernociception in rats and investigated the involvement of different mechanisms. Male Wistar rats were pretreated with injection (sc) of saline or Gc-FI 1h before intra- TMJ injection of formalin to evaluate the nociception. The results showed that pretreatment with Gc-FI significantly reduced formalin-induced nociceptive behavior. Moreover, the antinociceptive effect of the Gc-FI was blocked by naloxone (a non-selective opioid antagonist), suggesting the involvement of opioids selective receptors. Thus, the pretreatment with selective opioids receptors antagonists, reversed the antinociceptive effect of the Gc-FI in the TMJ. The Gc-FI antinociceptive effect depends on the nitric oxide/cyclic GMP/protein kinase G/ATP-sensitive potassium channel (NO/cGMP/PKG/K+ATP) pathway because it was prevented by pretreatment with inhibitors of nitric oxide synthase, guanylate cyclase enzyme, PKG and a K+ATP blocker. In addition, after inhibition with a specific heme oxygenase-1 (HO-1) inhibitor, the antinociceptive effect of the Gc-FI was not observed. Collectively, these data suggest that the antinociceptive effect induced by Gc-FI is mediated by μ/δ/κ-opioid receptors and by activation NO/cGMP/PKG/K+ATP channel pathway, besides of HO-1.

Keywords: Antinociception; Seaweed; Sulfated polysaccharide.

MeSH terms

  • Analgesics / chemistry
  • Analgesics / isolation & purification
  • Analgesics / pharmacology
  • Animals
  • Cyclic GMP / metabolism
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Formaldehyde / pharmacology
  • Gracilaria / chemistry*
  • Heme Oxygenase-1 / metabolism
  • Interleukin-10 / metabolism
  • KATP Channels / metabolism
  • Male
  • Nociception / drug effects
  • Plant Extracts / chemistry*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Opioid / metabolism
  • Seaweed / chemistry*
  • Serotonin / pharmacology
  • Signal Transduction / drug effects
  • Sulfates / chemistry*
  • Temporomandibular Joint / cytology
  • Temporomandibular Joint / drug effects*
  • Temporomandibular Joint / metabolism
  • Trigeminal Ganglion / drug effects
  • Trigeminal Ganglion / metabolism

Substances

  • Analgesics
  • KATP Channels
  • Plant Extracts
  • Receptors, Opioid
  • Sulfates
  • Interleukin-10
  • Formaldehyde
  • Serotonin
  • Heme Oxygenase-1
  • Cyclic GMP-Dependent Protein Kinases
  • Cyclic GMP