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A combination of gabapentin and morphine mediates enhanced inhibitory effects on dorsal horn neuronal responses in a rat model of neuropathy.
Anesthesiology. 2002 Mar; 96(3):633-40.A

Abstract

BACKGROUND

Peripheral nerve damage can result in severe, long-lasting pain accompanied by sensory deficits. This neuropathic pain remains a clinical problem, and effective morphine analgesia is often limited by intolerable side effects. The antiepileptic gabapentin has recently emerged as an alternative chronic pain treatment. Improved management of the diverse symptoms and mechanisms of neuropathic pain may arise from combination therapy, based on multiple pharmacologic targets and low drug doses.

METHODS

The authors used the Kim and Chung rodent model of neuropathy to induce mechanical and cold allodynia in the ipsilateral hind paw. In vivo electrophysiologic techniques were subsequently used to record evoked dorsal horn neuronal responses in which the effects of systemic morphine and gabapentin were investigated, both individually and in combination.

RESULTS

Morphine (1 and 4 mg/kg) inhibited neuronal responses of control rats but not after neuropathy. Gabapentin (10 and 20 mg/kg) inhibited neuronal responses in nerve injured rats and to a lesser extent in sham rats but not in naive rats. In the presence of gabapentin (ineffective low dose of 10 mg/kg), morphine (1 and 3 mg/kg) mediated significant inhibitory effects in all experimental groups, with the greatest inhibitions observed in spinal nerve-ligated and sham-operated rats. After neuropathy, inhibitions mediated by morphine were significantly increased in the presence of gabapentin compared with morphine alone.

CONCLUSIONS

After spinal nerve ligation, the inhibitory effects of systemic morphine on evoked dorsal horn neuronal responses are reduced compared with control, whereas the effectiveness of systemic gabapentin is enhanced. In combination with low-dose gabapentin, significant improvement in the effectiveness of morphine is observed, which demonstrates a clinical potential for the use of morphine and gabapentin combinational treatment for neuropathic pain.

Authors+Show Affiliations

Department of Pharmacology, University College London, London, United Kingdom. e,matthews@ucl.ac.ukNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11873039

Citation

Matthews, Elizabeth A., and Anthony H. Dickenson. "A Combination of Gabapentin and Morphine Mediates Enhanced Inhibitory Effects On Dorsal Horn Neuronal Responses in a Rat Model of Neuropathy." Anesthesiology, vol. 96, no. 3, 2002, pp. 633-40.
Matthews EA, Dickenson AH. A combination of gabapentin and morphine mediates enhanced inhibitory effects on dorsal horn neuronal responses in a rat model of neuropathy. Anesthesiology. 2002;96(3):633-40.
Matthews, E. A., & Dickenson, A. H. (2002). A combination of gabapentin and morphine mediates enhanced inhibitory effects on dorsal horn neuronal responses in a rat model of neuropathy. Anesthesiology, 96(3), 633-40.
Matthews EA, Dickenson AH. A Combination of Gabapentin and Morphine Mediates Enhanced Inhibitory Effects On Dorsal Horn Neuronal Responses in a Rat Model of Neuropathy. Anesthesiology. 2002;96(3):633-40. PubMed PMID: 11873039.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A combination of gabapentin and morphine mediates enhanced inhibitory effects on dorsal horn neuronal responses in a rat model of neuropathy. AU - Matthews,Elizabeth A, AU - Dickenson,Anthony H, PY - 2002/3/2/pubmed PY - 2002/4/18/medline PY - 2002/3/2/entrez SP - 633 EP - 40 JF - Anesthesiology JO - Anesthesiology VL - 96 IS - 3 N2 - BACKGROUND: Peripheral nerve damage can result in severe, long-lasting pain accompanied by sensory deficits. This neuropathic pain remains a clinical problem, and effective morphine analgesia is often limited by intolerable side effects. The antiepileptic gabapentin has recently emerged as an alternative chronic pain treatment. Improved management of the diverse symptoms and mechanisms of neuropathic pain may arise from combination therapy, based on multiple pharmacologic targets and low drug doses. METHODS: The authors used the Kim and Chung rodent model of neuropathy to induce mechanical and cold allodynia in the ipsilateral hind paw. In vivo electrophysiologic techniques were subsequently used to record evoked dorsal horn neuronal responses in which the effects of systemic morphine and gabapentin were investigated, both individually and in combination. RESULTS: Morphine (1 and 4 mg/kg) inhibited neuronal responses of control rats but not after neuropathy. Gabapentin (10 and 20 mg/kg) inhibited neuronal responses in nerve injured rats and to a lesser extent in sham rats but not in naive rats. In the presence of gabapentin (ineffective low dose of 10 mg/kg), morphine (1 and 3 mg/kg) mediated significant inhibitory effects in all experimental groups, with the greatest inhibitions observed in spinal nerve-ligated and sham-operated rats. After neuropathy, inhibitions mediated by morphine were significantly increased in the presence of gabapentin compared with morphine alone. CONCLUSIONS: After spinal nerve ligation, the inhibitory effects of systemic morphine on evoked dorsal horn neuronal responses are reduced compared with control, whereas the effectiveness of systemic gabapentin is enhanced. In combination with low-dose gabapentin, significant improvement in the effectiveness of morphine is observed, which demonstrates a clinical potential for the use of morphine and gabapentin combinational treatment for neuropathic pain. SN - 0003-3022 UR - https://www.unboundmedicine.com/medline/citation/11873039/A_combination_of_gabapentin_and_morphine_mediates_enhanced_inhibitory_effects_on_dorsal_horn_neuronal_responses_in_a_rat_model_of_neuropathy_ L2 - https://pubs.asahq.org/anesthesiology/article-lookup/doi/10.1097/00000542-200203000-00020 DB - PRIME DP - Unbound Medicine ER -