Osthole alleviated diabetic neuropathic pain mediated by the P2X4 receptor in dorsal root ganglia

Brain Res Bull. 2018 Sep:142:289-296. doi: 10.1016/j.brainresbull.2018.08.008. Epub 2018 Aug 14.

Abstract

Diabetes mellitus (DM) is considered the primary cause of neuropathic pain. Osthole (7-methoxy-8[3-methylpent 2-enyl]coumarin) is a component extracted from Cnidium monnieri (L.) cusson plant seeds and has anti-inflammatory and anti-oxidative properties. The aim of the present study was to investigate the effects of osthole on diabetic neuropathic pain (DNP) involving the P2X4 receptor on satellite glial cells (SGCs) in the dorsal root ganglia (DRG) of type 2 diabetic rats. These data showed that the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in DM rats were lower than those in control rats. MWT and TWL in DM rats treated with osthole were higher compared with those in untreated DM rats. The expression levels of P2X4 mRNA and protein in the DRG of DM rats were higher compared with those in the control rats, while those in DM rats treated with osthole were significantly lower compared with those in the untreated DM rats. Osthole treatment decreased the co-expression levels of P2X4 and glial fibrillary acidic protein (GFAP) and reduced the up-regulated expression of interleukin-1 beta (IL-1β), tumour necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF) and phosphorylated-p38MAPK and enhanced the down-regulation of IL-10 in DM rats. Thus, osthole treatment may act on the P2X4 receptor to alleviate the mechanical and thermal hyperalgesia in DM rats.

Keywords: Diabetic neuropathic pain; Dorsal root ganglia; Osthole; P2X(4)receptor; Satellite glial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Coumarins / pharmacology*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / pathology
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / pathology
  • Hyperalgesia / drug therapy
  • Hyperalgesia / metabolism
  • Hyperalgesia / pathology
  • Hypoglycemic Agents / pharmacology
  • Male
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Neuralgia / pathology
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Purinergic P2X Receptor Antagonists / pharmacology
  • Random Allocation
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2X4 / metabolism*
  • Up-Regulation / drug effects

Substances

  • Analgesics
  • Coumarins
  • Hypoglycemic Agents
  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X4
  • osthol