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Opiates and antioxidants inhibit tactile‐evoked allodynia
Author(s) -
Crisp Terriann,
Giles Jennifer R.,
Finnerty Edward P.
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-b
Subject(s) - allodynia , morphine , pharmacology , gabapentin , neuropathic pain , anesthesia , medicine , hyperalgesia , chemistry , nociception , receptor , alternative medicine , pathology
Reactive oxygen species contribute to the development and maintenance of central sensitization and pathological pain states. Oxidative metabolites are thought to inhibit the reuptake of spinal glutamate, which accumulates in the synapse and acts as an excitatory mediator of tactile‐evoked allodynia. In this study, the antiallodynic efficacy of combination therapy with antioxidants (α‐lipoic acid) and opiates (morphine sulfate) was investigated in 2–4 and 24–26 month old rats. Peripheral nerve injury was induced using the L 5 spinal nerve ligation (SNL) model, and calibrated von Frey filaments were used to measure changes in paw withdrawal threshold values (tactile‐evoked allodynia). Dose‐response curves and time course data were generated for morphine (1, 3 or 10 mg/kg, i.p.) or α‐lipoic acid (30, 100 or 300 mg/kg, i.p.) in rats with peripheral nerve injury versus animals with sham lesions. Subanalgesic doses of morphine were then combined with α‐lipoic acid, and the antiallodynic effects both agents were tested. The results revealed that the 10 mg/kg dose of i.p. morphine reversed tactile allodynia for at least 120 minutes. Intraperitoneal (i.p.) doses of morphine (3 mg/kg) or α‐lipoic acid (100 mg/kg) were relatively ineffective at reversing tactile‐evoked allodynia when administered alone on day‐3 post‐SNL. Combination subanalgesic doses of α‐lipoic acid and morphine completely reversed tactile‐evoked allodynia for at least two hours when administered together. This pharmacological additivity/synergism suggests that combination therapy with subanalgesic doses of opiates and antioxidants may be efficacious for treating patients with neuropathic pain conditions.