Skip to main content
Top
Published in: Inflammopharmacology 1/2018

01-02-2018 | Original Article

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

Authors: Dong Wook Lim, Jae Goo Kim, Eun Yeong Lim, Yun Tai Kim

Published in: Inflammopharmacology | Issue 1/2018

Login to get access

Abstract

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.
Literature
go back to reference Ahmad M, Saleem S, Ahmad AS, Ansari MA, Yousuf S, Hoda MN, Islam F (2005) Neuroprotective effects of Withania somnifera on 6-hydroxydopamine induced Parkinsonism in rats. Hum Exp Toxicol 24:137–147CrossRefPubMed Ahmad M, Saleem S, Ahmad AS, Ansari MA, Yousuf S, Hoda MN, Islam F (2005) Neuroprotective effects of Withania somnifera on 6-hydroxydopamine induced Parkinsonism in rats. Hum Exp Toxicol 24:137–147CrossRefPubMed
go back to reference Backonja MM (1999) Gabapentin monotherapy for the symptomatic treatment of painful neuropathy: a multicenter, double-blind, placebo-controlled trial in patients with diabetes mellitus Epilepsia 40(Suppl 6):S57–S59 (discussion S73–S54) Backonja MM (1999) Gabapentin monotherapy for the symptomatic treatment of painful neuropathy: a multicenter, double-blind, placebo-controlled trial in patients with diabetes mellitus Epilepsia 40(Suppl 6):S57–S59 (discussion S73–S54)
go back to reference Bhattacharya SK, Satyan KS, Chakrabarti A (1997a) Effect of Trasina, an Ayurvedic herbal formulation, on pancreatic islet superoxide dismutase activity in hyperglycaemic rats. Indian J Exp Biol 35:297–299PubMed Bhattacharya SK, Satyan KS, Chakrabarti A (1997a) Effect of Trasina, an Ayurvedic herbal formulation, on pancreatic islet superoxide dismutase activity in hyperglycaemic rats. Indian J Exp Biol 35:297–299PubMed
go back to reference Bhattacharya SK, Satyan KS, Ghosal S (1997b) Antioxidant activity of glycowithanolides from Withania somnifera. Indian J Exp Biol 35:236–239PubMed Bhattacharya SK, Satyan KS, Ghosal S (1997b) Antioxidant activity of glycowithanolides from Withania somnifera. Indian J Exp Biol 35:236–239PubMed
go back to reference Brennan TJ, Vandermeulen EP, Gebhart GF (1996) Characterization of a rat model of incisional pain. Pain 64:493–501CrossRefPubMed Brennan TJ, Vandermeulen EP, Gebhart GF (1996) Characterization of a rat model of incisional pain. Pain 64:493–501CrossRefPubMed
go back to reference Brodmerkel CM et al (2005) Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J Immunol 175:5370–5378CrossRefPubMed Brodmerkel CM et al (2005) Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J Immunol 175:5370–5378CrossRefPubMed
go back to reference Brudzynski SM, Chiu EM (1995) Behavioural responses of laboratory rats to playback of 22 kHz ultrasonic calls. Physiol Behav 57:1039–1044CrossRefPubMed Brudzynski SM, Chiu EM (1995) Behavioural responses of laboratory rats to playback of 22 kHz ultrasonic calls. Physiol Behav 57:1039–1044CrossRefPubMed
go back to reference De Bosscher K, Vanden Berghe W, Haegeman G (2003) The interplay between the glucocorticoid receptor and nuclear factor-kappa B or activator protein-1: molecular mechanisms for gene repression. Endocr Rev 24:488–522. doi:10.1210/er.2002-0006 CrossRefPubMed De Bosscher K, Vanden Berghe W, Haegeman G (2003) The interplay between the glucocorticoid receptor and nuclear factor-kappa B or activator protein-1: molecular mechanisms for gene repression. Endocr Rev 24:488–522. doi:10.​1210/​er.​2002-0006 CrossRefPubMed
go back to reference Decosterd I, Woolf CJ (2000) Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87:149–158CrossRefPubMed Decosterd I, Woolf CJ (2000) Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87:149–158CrossRefPubMed
go back to reference Grandhi A, Mujumdar AM, Patwardhan B (1994) A comparative pharmacological investigation of Ashwagandha and Ginseng. J Ethnopharmacol 44:131–135CrossRefPubMed Grandhi A, Mujumdar AM, Patwardhan B (1994) A comparative pharmacological investigation of Ashwagandha and Ginseng. J Ethnopharmacol 44:131–135CrossRefPubMed
go back to reference Hunter JC, Gogas KR, Hedley LR, Jacobson LO, Kassotakis L, Thompson J, Fontana DJ (1997) The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain. Eur J Pharmacol 324:153–160CrossRefPubMed Hunter JC, Gogas KR, Hedley LR, Jacobson LO, Kassotakis L, Thompson J, Fontana DJ (1997) The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain. Eur J Pharmacol 324:153–160CrossRefPubMed
go back to reference Knutson B, Burgdorf J, Panksepp J (1998) Anticipation of play elicits high-frequency ultrasonic vocalizations in young rats. J Comp Psychol 112:65–73CrossRefPubMed Knutson B, Burgdorf J, Panksepp J (1998) Anticipation of play elicits high-frequency ultrasonic vocalizations in young rats. J Comp Psychol 112:65–73CrossRefPubMed
go back to reference Knutson B, Burgdorf J, Panksepp J (2002) Ultrasonic vocalizations as indices of affective states in rats. Psychol Bull 128:961–977CrossRefPubMed Knutson B, Burgdorf J, Panksepp J (2002) Ultrasonic vocalizations as indices of affective states in rats. Psychol Bull 128:961–977CrossRefPubMed
go back to reference Kulkarni SK, Ninan I (1997) Inhibition of morphine tolerance and dependence by Withania somnifera in mice. J Ethnopharmacol 57:213–217CrossRefPubMed Kulkarni SK, Ninan I (1997) Inhibition of morphine tolerance and dependence by Withania somnifera in mice. J Ethnopharmacol 57:213–217CrossRefPubMed
go back to reference Miczek KA, Weerts EM, Vivian JA, Barros HM (1995) Aggression, anxiety and vocalizations in animals: GABAA and 5-HT anxiolytics. Psychopharmacology 121:38–56CrossRefPubMed Miczek KA, Weerts EM, Vivian JA, Barros HM (1995) Aggression, anxiety and vocalizations in animals: GABAA and 5-HT anxiolytics. Psychopharmacology 121:38–56CrossRefPubMed
go back to reference Portfors CV (2007) Types and functions of ultrasonic vocalizations in laboratory rats and mice. J Am Assoc Lab Anim Sci JAALAS 46:28–34PubMed Portfors CV (2007) Types and functions of ultrasonic vocalizations in laboratory rats and mice. J Am Assoc Lab Anim Sci JAALAS 46:28–34PubMed
go back to reference Richner M, Bjerrum OJ, Nykjaer A, Vaegter CB (2011) The spared nerve injury (SNI) model of induced mechanical allodynia in mice. J Vis Exp JOVE. doi:10.3791/3092 PubMed Richner M, Bjerrum OJ, Nykjaer A, Vaegter CB (2011) The spared nerve injury (SNI) model of induced mechanical allodynia in mice. J Vis Exp JOVE. doi:10.​3791/​3092 PubMed
go back to reference Singh B, Saxena AK, Chandan BK, Gupta DK, Bhutani KK, Anand KK (2001) Adaptogenic activity of a novel, withanolide-free aqueous fraction from the roots of Withania somnifera Dun. Phytother Res 15:311–318CrossRefPubMed Singh B, Saxena AK, Chandan BK, Gupta DK, Bhutani KK, Anand KK (2001) Adaptogenic activity of a novel, withanolide-free aqueous fraction from the roots of Withania somnifera Dun. Phytother Res 15:311–318CrossRefPubMed
go back to reference Singh N, Bhalla M, de Jager P, Gilca M (2011) An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Compl Altern Med 8:208–213. doi:10.4314/ajtcam.v8i5S.9 Singh N, Bhalla M, de Jager P, Gilca M (2011) An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Compl Altern Med 8:208–213. doi:10.​4314/​ajtcam.​v8i5S.​9
go back to reference Subbaraju GV, Vanisree M, Rao CV, Sivaramakrishna C, Sridhar P, Jayaprakasam B, Nair MG (2006) Ashwagandhanolide, a bioactive dimeric thiowithanolide isolated from the roots of Withania somnifera. J Nat Prod 69:1790–1792. doi:10.1021/np060147p CrossRefPubMed Subbaraju GV, Vanisree M, Rao CV, Sivaramakrishna C, Sridhar P, Jayaprakasam B, Nair MG (2006) Ashwagandhanolide, a bioactive dimeric thiowithanolide isolated from the roots of Withania somnifera. J Nat Prod 69:1790–1792. doi:10.​1021/​np060147p CrossRefPubMed
go back to reference Wagner R, Janjigian M, Myers RR (1998) Anti-inflammatory interleukin-10 therapy in CCI neuropathy decreases thermal hyperalgesia, macrophage recruitment, and endoneurial TNF-alpha expression. Pain 74:35–42CrossRefPubMed Wagner R, Janjigian M, Myers RR (1998) Anti-inflammatory interleukin-10 therapy in CCI neuropathy decreases thermal hyperalgesia, macrophage recruitment, and endoneurial TNF-alpha expression. Pain 74:35–42CrossRefPubMed
go back to reference Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K (2002) Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull (Tokyo) 50:760–765CrossRef Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K (2002) Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull (Tokyo) 50:760–765CrossRef
Metadata
Title
Antihyperalgesic effects of ashwagandha (Withania somnifera root extract) in rat models of postoperative and neuropathic pain
Authors
Dong Wook Lim
Jae Goo Kim
Eun Yeong Lim
Yun Tai Kim
Publication date
01-02-2018
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 1/2018
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-017-0389-1

Other articles of this Issue 1/2018

Inflammopharmacology 1/2018 Go to the issue