Water extract of Notopterygium incisum alleviates cold allodynia in neuropathic pain by regulation of TRPA1

J Ethnopharmacol. 2023 Apr 6:305:116065. doi: 10.1016/j.jep.2022.116065. Epub 2022 Dec 29.

Abstract

Ethnopharmacological relevance: Neuropathic pain can be debilitating and drastically affects the quality of life of those patients suffering from this condition. The Chinese herb Notopterygium incisum Ting ex H.T. Chang has long been used to disperse "cold". One under examined clinical feature of neuropathic pain is sensitivity to cold. Patients with neuropathic pain or arthritis usually describe a worsening of symptoms during the winter.

Aims of this study: We proposed to test the hypothesis that Notopterygium incisum has a positive effect on the cold sensitivity found in neuropathic pain.

Materials and methods: In this study, we established chronic constriction injury (CCI) and cisplatin induced neuropathic pain mice models. Behavioral experiments and physiological examination methods were employed to investigate the effect of water extract of Notopterygium incisum (WN) on cold pain.

Results: We found WN reduced cold pain and allyl isothiocyanate (AITC, Transient Receptor Potential A1 (TRPA1 agonist)) induced pain. WN inhibited AITC induced calcium response in HEK 293 cells transfected with TRPA1 and dorsal root ganglion (DRG) neurons. Moreover, we found that oral administration of WN reduced cold allodynia and mechanical allodynia caused by (CCI) and cisplatin induced neuropathic pain. We also observed that oral administration of WN decreased responses to AITC in DRG neurons as well as expression of TRPA1 in the WN treated neuropathic pain model.

Conclusions: The present study provide evidence that Notopterygium incisum alleviates cold allodynia in CCI and cisplatin induced neuropathic pain mouse models. WN alleviated neuropathic pain induced cold allodynia via directly modulating TRPA1. Our findings identify WN as a promising candidate for treating neuropathic pain that highlights a new mechanism of Notopterygium incisum on 'disperse cold'.

Keywords: Cold pain; DRG; Neuropathic pain; Notopterygium incisum; TRPA1.

MeSH terms

  • Animals
  • Cisplatin
  • Ganglia, Spinal / metabolism
  • HEK293 Cells
  • Humans
  • Hyperalgesia* / drug therapy
  • Hyperalgesia* / metabolism
  • Mice
  • Neuralgia* / drug therapy
  • Neuralgia* / metabolism
  • Quality of Life
  • TRPA1 Cation Channel / metabolism

Substances

  • 2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate
  • Cisplatin
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Trpa1 protein, mouse