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Aging and the anti‐allodynic efficacy of combination treatment with opiates and antioxidants
Author(s) -
Crisp Terriann,
Giles Jennifer R.,
Egli Shan D.,
Henry Matthew K.,
Finnerty Edward P.
Publication year - 2008
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.22.1_supplement.1125.8
Subject(s) - medicine , morphine , pharmacology , neuropathic pain , lipoic acid , allodynia , anesthesia , peripheral , hyperalgesia , antioxidant , nociception , chemistry , receptor , biochemistry
Pharmacological studies were undertaken to investigate age‐related differences in the efficacy of co‐administration of morphine and antioxidants (á‐lipoic acid) to reverse the allodynic symptoms of peripheral nerve injury. The L‐5 spinal nerve was ligated to induce peripheral nerve injury in young and aged rats (2–4 or 26–30 months old, respectively). Calibrated von Frey filaments were used to measure changes in paw withdrawal threshold. Dose‐response curves were generated for morphine sulfate (1, 3 or 10 mg/kg, i.p.) or á‐lipoic acid (30, 100 or 300 mg/kg, i.p.) in young and aged rats prior to and following L‐5 spinal nerve ligation. In subsequent experiments, combination subanalgesic doses of morphine and á‐lipoic acid were administered and the antiallodynic efficacy of these agents was assessed. Results revealed that, in young animals, doses of morphine (1 mg/kg i.p.) or á‐lipoic acid (100 mg/kg i.p.) that were ineffective at reversing tactile‐evoked allodynia when administered alone were highly efficacious at inhibiting the allodynic symptoms of peripheral nerve injury when co‐administered. In the aged cohort of rats, the results were similar. These data support a mediatory role of oxidative metabolites in persistent pain, and reinforce the potential therapeutic usefulness of combination opiate/antioxidant therapy for treating humans with persistent pain of neuropathic origin.