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Norketamine in combination with morphine for inflammatory pain
Author(s) -
Johnson Jaime K,
Wala Elzbieta P,
Crooks Peter A,
Dorfling Lizemari,
Holtman Joseph R
Publication year - 2007
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.21.5.a412
Subject(s) - nociception , morphine , pharmacology , opioid , nmda receptor , ketamine , sensitization , medicine , (+) naloxone , antagonist , neuropathic pain , anesthesia , receptor , immunology
Both opioids (i.e. morphine, MOR) and NMDA receptor antagonists (i.e. ketamine, KET) have activity in the rat formalin nociceptive test. This model has two phases representing inflammatory nocicepive pain (phase 1) and pain involving central sensitization mechanism (phase 2). There are significant side effects issues related to the use of these drugs chronically for pain. One approach to increase efficacy, block opioid tolerance development and limit side effects has been to combine low doses of an opioid and an NMDA antagonist. This was done in the present study were MOR was co‐administered with the enantiomers of norketamine‐HCL (NKET), the major metabolite of KET. We previously found that NKET has fever side effects than KET. Formalin‐induced nociceptive behavior (flinches) was found to consist of an early (nociceptive) and a late (central sensitization) phases in rats. Both S(+)‐NKET (0.01–1mg/kg) and R(−)‐NKET (0.5–1.5mg/kg) enhanced MOR (0.5mg/kg) analgesia, in a dose‐related manner, during the late phase [the S(+) > the R(−)]. In addition, S(+)‐NKET potentiated the effect of MOR in the early phase. These data suggest that MOR in combination with S(+)‐NKET (low doses) may have potential as a novel combination therapy for treatment of pain due to both nociceptive and neuropathic etiologies. Support: NIDA R‐42 DA017529 ‐02A1 and KSEF‐949‐RDE‐008 (JRH)