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The antinociceptive effect of S(‐)‐Norketamine in an inflammatory pain model
Author(s) -
Johnson Jaime K,
Whitney Justin A,
Wala Elzbieta P,
Holtman Joseph R
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a241-d
Subject(s) - licking , nociception , analgesic , nmda receptor , pharmacology , anesthesia , saline , ketamine , antagonist , medicine , neuropathic pain , chronic pain , receptor antagonist , receptor , psychiatry
Adequate management of chronic pain remains a significant medical problem. N‐methyl‐D‐aspartate (NMDA) receptor antagonists are potential drugs for chronic pain. However, the use of ketamine (KET), the only clinically available NMDA receptor antagonist, has been limited due to psychomimetic, sedative and motor effects. Our previous study demonstrated that a metabolite of KET, S(‐)‐norketamine (norKET), was approximately equipotent with KET in a rodent model of neuropathic pain. Importantly, the side effects were less pronounced for norKET than KET in rats. In the present study we examined whether norKET has an antinociceptive effect in an inflammatory pain model (paw formalin test). Male Sprague‐Dawley rats were treated with either norKET (0.5, 1, 5 mg/kg, IP), KET (0.5, 1, 5 mg/kg, IP) or saline 15 minutes prior to a 50 mcl injection of 5% formalin in the dorsal surface of the hind paw. Flinching and licking were recorded during 5‐minute intervals for 60 minutes. Formalin‐induced nociceptive behavior consisted of an early phase (0–10 min) and a late phase (within 20 min) in control (saline) rats. NorKET attenuated in a dose‐related fashion formalin‐induced flinching during the late (tonic) phase. KET produced a similar effect. Neither norKET or KET affected the early (acute) phase of the formalin test. The present data together with our previous findings suggest that norKET has potential as a novel NMDA antagonist analgesic drug for treatment of a wide spectrum of chronic pain including both neuropathic and tonic inflammatory pain. Support: UK Science Outreach Program (JAW) and NIDA K12 BIRCWH Program (JRH).