Effect of delayed intrathecal administration of capsaicin on neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats
Kun Zhang,1 Somayaji Ramamurthy,1 Thomas J Prihoda,2 Maxim S Eckmann1
1Department of Anesthesiology, 2Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Purpose: The current study was designed to examine the antinociceptive effect of intrathecally administered capsaicin, a transient receptor potential vanilloid 1 receptor agonist, in a rat model of neuropathic pain induced by unilateral sciatic nerve chronic constriction injury.
Methods: Male adult Sprague Dawley rats were randomly assigned to six groups, and all rats underwent unilateral sciatic nerve chronic constriction injury. Two weeks after injury, five groups received intrathecal administration of either capsaicin in three different dosing regimens or equal volumes of vehicle. The other group received intrathecal capsaicin on the third day after nerve injury. The antinociceptive effect of capsaicin was assessed by measuring the capsaicin-induced change in thermal and mechanical response thresholds.
Results: Capsaicin (150–300 µg/100–200 µL), when administered by fast infusion or chronic infusions at 8 µL/hour or 1 µL/hour, attenuated thermal hyperalgesia as indicated by significantly prolonging paw withdrawal latency to noxious thermal stimulation. The antinociceptive effect of capsaicin was more profound in the injured limb compared to that in the uninjured limb. When capsaicin was administered on the third day after nerve injury, it failed to attenuate thermal hyperalgesia. No significant effect on the mechanical response threshold was observed with intrathecally administered capsaicin.
Conclusion: Our data suggest that intrathecal capsaicin could significantly attenuate thermal hyperalgesia, depending on the time when the drug is given after nerve injury, and that the antinociceptive efficacy of intrathecal capsaicin positively correlates with the previously reported dynamic profile of spinal transient receptor potential vanilloid 1 activity after nerve injury.
Keywords: hyperalgesia, TRPV1, paw withdrawal latency, paw withdrawal threshold
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