Antiallodynic Effects of Intrathecal Areca Nut for Spinal Nerve-Ligated and Chemotherapy-Induced Neuropathic Pain in Rats

Pharmacology. 2018;102(5-6):332-338. doi: 10.1159/000492394. Epub 2018 Oct 10.

Abstract

This study examined the effects of intrathecal areca nut on spinal nerve-ligated and chemotherapy-induced neuropathic pain (NP), and investigated the relevance of spinal 5-hydroxytryptamine (5-HT) and α2-adrenergic receptors to those effects. For drug administration, intrathecal catheters were inserted into the subarachnoid space of male Sprague-Dawley rats. NP was induced either by spinal nerve ligation (left spinal nerves L5 and L6) or by chemotherapeutic injection (intraperitoneal cisplatin, 2 mg/kg/day, once daily for 4 days). Paw withdrawal thresholds (PWT) were mechanically assessed using von Frey filaments. The involvement of 5-HT and α2-adrenergic receptors in antiallodynia was determined using antagonists with the following receptor specificities: nonselective 5-HT (dihydroergocristine), 5-HT7 (SB269970), nonselective α2-adrenoceptor (yohimbine), α-2A (BRL 44408), α-2B (ARC 239), and α-2C (JP 1302). Intrathecal areca nut significantly increased the PWT in both spinal nerve-ligated and chemotherapy-induced NP (‡ p < 0.001). Intrathecal dihydroergocristine, SB269970, yohimbine, BRL 44408, ARC 239, and JP 1302 significantly reversed the antiallodynic effects of areca nut in both NP states (‡ p < 0.001). Collectively, intrathecal areca nut suppressed mechanical allodynia induced by spinal nerve ligation and cisplatin injection. Furthermore, spinal 5-HT7 receptor and α2A, α2B, and α2C-adrenoceptors contributed to the antiallodynic effects of areca nut.

Keywords: 5-hydroxytryptamine receptors; Antiallodynia; Areca nut; Neuropathic pain; Spinal cord; α2-adrenoceptors.

MeSH terms

  • Adrenergic alpha-2 Receptor Antagonists / pharmacology
  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Areca*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects*
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / metabolism
  • Injections, Spinal
  • Ligation
  • Male
  • Neuralgia / chemically induced
  • Neuralgia / drug therapy*
  • Neuralgia / etiology
  • Neuralgia / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Receptors, Serotonin / metabolism
  • Serotonin Antagonists / pharmacology
  • Spinal Cord / drug effects
  • Spinal Cord / surgery
  • Spinal Nerves

Substances

  • Adrenergic alpha-2 Receptor Antagonists
  • Analgesics, Non-Narcotic
  • Receptors, Adrenergic, alpha-2
  • Receptors, Serotonin
  • Serotonin Antagonists
  • serotonin 7 receptor
  • Cisplatin