Antihyperalgesic effects of ashwagandha (Withania somnifera root extract) in rat models of postoperative and neuropathic pain

The root of Withania somnifera, commonly known as ashwagandha, is a traditional herb in the Indian Ayurvedic system of medicine and is used as a tonic. Here, we investigated whether W. somnifera root extract exhibits analgesic effects in plantar incision (PI) and spared nerve injury (SNI) rat models. Mechanical withdrawal threshold (MWT) was measured by von Frey filaments, and pain-related behavior was determined after operation by ultrasonic vocalization (USV) measurements. Indeed, we examined interferon-γ (IFN-γ) and interleukin-10 (IL-10) levels in the isolated dorsal root ganglia (DRG) following SNI in rats using an ELISA cytokine assay. MWT significantly increased 6 and 24 h after PI in rats receiving W. somnifera root extracts (100 and 300 mg/kg). Furthermore, the number of 22-27-kHz USV, which are a distress response, was significantly reduced at 6 and 24 h after PI in W. somnifera-treated rats (100 and 300 mg/kg). SNI-induced hyperalgesia and cytokine levels were significantly alleviated after treating with W. somnifera root extracts (100 and 300 mg/kg) for 15 continuous days. The main active compound, withaferin A, from the W. somnifera root extract has shown the CC chemokine family Receptor 2 (CCR2) antagonistic effects on monocyte chemoattractant protein-1 (MCP-1)-induced Ca²⁺ response in CCR2 stable cell line. These results indicate that W. somnifera root extract has a potential analgesic effect in rat models for both postoperative and neuropathic pain and shows potential as a drug or supplement for the treatment of pain.