Anti-allodynic and Anti-hyperalgesic effects of an ethanolic extract and xylopic acid from the fruits of Xylopia aethiopica in murine models of neuropathic pain

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Abstract

Background:

Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including headache and neuralgia. An animal model of vincristine-induced sensory neuropathy was developed after repeated intraperitoneal injection in rats and used in the present work to study the effects of the ethanolic extract of X. aethiopica (XAE) and its diterpene xylopic acid (XA) in vincristine-induced neuropathic pain.

Materials and Methods:

Vincristine (0.1 mg kg ^-1 day ^-1) was administered during two cycles of five consecutive days to induce chemotherapy-induced neuropathic pain. Static tactile anti-allodynic, anti-hyperalgesic, and cold anti-allodynic effects of XAE (30-300 mg kg ^-1) and XA (10-100 mg kg ^-1) were assessed using Von Frey filaments of bending forces of 4, 8, and 15 g, the Randall-Selitto paw pressure test, and cold water (4.5°C), respectively.

Results:

Administration of vincristine caused the development of allodynia and hyperalgesia with no significant motor deficit, spontaneous pain, and foot deformity. XAE (30-300 mg kg ^-1) and XA (10-100 mg kg ^-1) exhibited anti-hyperalgesic, tactile, and cold anti-allodynic properties with XA exhibiting greater potency than XAE. Pregabalin (10-100 mg kg ^-1) used as control produced similar effect.

Conclusion:

These findings establish the anti-allodynic and anti-hyperalgesic effects of the ethanolic fruit XAE and its major diterpene XA in vincristine-induced neuropathtic pain.

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Most cited references 37

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Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy.

Sarah Flatters, Gary Bennett (2004)

Paclitaxel (Taxol) is one of the most effective and frequently used chemotherapeutics for the treatment of solid tumours. However, paclitaxel produces peripheral neurotoxicity with patients reporting sensory abnormalities and neuropathic pain during and often persisting after paclitaxel therapy. The mechanisms underlying this dose-limiting side effect are currently unknown and there are no validated drugs for its prevention or control. Male Sprague-Dawley rats received four intraperitoneal (i.p.) injections on alternate days of 2 mg/kg paclitaxel. Behavioural assessment using von Frey filaments and acetone showed that such paclitaxel treatment induced a pronounced mechanical and cold allodynia/hyperalgesia. Thus these studies aim to test potential analgesics on established paclitaxel-induced pain. Paclitaxel-induced pain appears to be relatively resistant to opioid therapy i.p. 4 mg/kg morphine was ineffective and i.p. 8 mg/kg morphine only elicited up to a 50% reversal of mechanical allodynia/hyperalgesia. Interestingly, a maximally tolerated dose (i.p. 0.2 mg/kg) of the potent NMDA receptor antagonist MK-801 produced no significant reversal of the mechanical allodynia/hyperalgesia suggesting that NMDA receptors have little role in paclitaxel-induced pain. Ethosuximide (i.p. 450 mg/kg) an anti-epileptic and relatively selective T-type calcium channel blocker elicited a near complete reversal of mechanical allodynia/hyperalgesia. Repetitive dosing with ethosuximide (i.p. 100 or 300 mg/kg daily for 3 days) showed a dose-related consistent reversal of mechanical allodynia/hyperalgesia with no evidence of tolerance. Ethosuximide (i.p. 300 mg/kg) also reversed paclitaxel-induced cold allodynia and vincristine-induced mechanical allodynia/hyperalgesia. These data suggest that T-type calcium channels may play a role in chemotherapy-induced neuropathy and moreover identify ethosuximide as a new potential treatment for chemotherapy-induced pain.

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Abeta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals.

Laiche Djouhri, Sally N. Lawson (2004)

The existence of nociceptors with Abeta-fibers has often been overlooked, and many textbooks endorse the view that all nociceptors have either C- or Adelta-fibers. Here we review evidence starting from the earliest descriptions of A-fiber nociceptors, which clearly indicates that a substantial proportion of cutaneous/somatic afferent A-fiber nociceptors conduct in the Abeta conduction velocity (CV) range in all species in which CV was carefully examined, including mouse, rat, guinea pig, cat and monkey. Reported proportions of A-fiber nociceptors with Abeta-fibers vary from 18% to 65% in different species, usually >50% in rodents. In rat, about 20% of all somatic afferent neurons with Aalpha/beta-fibers were nociceptive. Distributions of CVs of A-fiber nociceptors usually appear unimodal, with a median/peak in the upper Adelta or lower Abeta CV range. We find no evidence to suggest discontinuous differences in electrophysiological or cytochemical properties of Adelta and Abeta nociceptors, rather there are gradual changes in relation to CV. However, some functional differences have been reported. In cat, A-fiber nociceptors with lower mechanical thresholds (moderate pressure receptors) tend to have faster CVs [P.R. Burgess, D. Petit, R.M. Warren. Receptor types in cat hairy skin supplied by myelinated fibers. J. Neurophysiol. 31 (1968) 833-848]. In primate (monkey) A-fiber nociceptors that responded to heat were divided into type I A mechano-heat (AMH) units (Adelta and Abeta CVs) with lower mechanical and higher heat thresholds and may include moderate pressure receptors, and type II AMH units (Adelta CVs) with higher mechanical/lower heat thresholds. It is important that the existence of Abeta nociceptors is recognised, because assumptions that fast conducting, large diameter afferents are always low threshold mechanoreceptors might lead/have led to misinterpretations of data.

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Spontaneous discharge originates in the dorsal root ganglion at the onset of a painful peripheral neuropathy in the rat.

Keith C. Kajander, Satoshi Wakisaka, Gary J Bennett (1992)

The activity of myelinated primary afferents was recorded from the dorsal roots 1-3 days after creation of a painful peripheral neuropathy in rats. The effects on spontaneous discharge of acute transections at various points along the injured sciatic nerve and the dorsal root were determined, as were the effects of K+ channel blockers applied topically to two putative sites of impulse origin: the injured region of the nerve and the dorsal root ganglion (DRG). Transections just proximal to the nerve injury and just distal to the DRG failed to halt the discharge, but spontaneous discharge disappeared when the transection was made just proximal to the DRG (i.e. between the DRG and recording electrode). K+ channel blockers (4-aminopyridine and gallamine triethiodide) applied to the DRG increased the frequency of spontaneous discharge or initiated activity from silent fibers. Applications of K+ channel blockers to the injured region of the nerve were without effect. Thus, the spontaneous discharge and the sensitivity to K+ channel blockade seen in A beta and A delta primary afferents at the time of the onset of the neuropathic pain syndrome appear to originate in the DRG.

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Author and article information

Journal

Journal ID (nlm-ta): Pharmacognosy Res

Journal ID (iso-abbrev): Pharmacognosy Res

Journal ID (publisher-id): PR

Title: Pharmacognosy Research

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 0976-4836

ISSN (Electronic): 0974-8490

Publication date (Print): Apr-Jun 2014

Volume: 6

Issue: 2

Pages: 172-179

Affiliations

[1] Department of Biomedical and Forensic Sciences, School of Biological Science, University of Cape Coast, Cape Coast, Ghana

[1 ] Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

[2 ] Department of Pharmaceutical chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Author notes

Address for correspondence: Prof. Eric Woode, Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Republic of Ghana. E-mail: ewoode.pharm@ 123456knust.edu.gh

Article

Publisher ID: PR-6-172

DOI: 10.4103/0974-8490.129041

PMC ID: 3996755

PubMed ID: 24761123

SO-VID: b963cdef-b5f8-4c60-8903-37a2f8c11e78

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 14 July 2013

Date revision received : 04 September 2013

Date accepted : 18 March 2014

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Anti-allodynic and Anti-hyperalgesic effects of an ethanolic extract and xylopic acid from the fruits of Xylopia aethiopica in murine models of neuropathic pain

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Abstract

Background:

Materials and Methods:

Results:

Conclusion:

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RNA drug delivery

Most cited references 37

Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy.

Abeta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals.

Spontaneous discharge originates in the dorsal root ganglion at the onset of a painful peripheral neuropathy in the rat.

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Cited by 16

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