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Differential pharmacological modulation of the spontaneous stimulus-independent activity in the rat spinal cord following peripheral nerve injury.
Exp Neurol. 2006 Mar; 198(1):72-80.EN

Abstract

Peripheral nerve injury is a significant clinical problem that is often difficult to treat. The major clinical symptoms are numbness, tactile and cooling allodynia, hyperalgesias as well as ongoing pain. In animal models of neuropathy, abnormal responses to applied (or evoked) stimuli can be gauged, but spontaneous pain, a major clinical issue, has proved very difficult to assess. In neuropathic animals, spinal neuronal hyperexcitability indicative of peripheral and central changes with high levels of spontaneous neuronal firing has been reported. This latter stimulus-independent firing of sensory neurones may be a measure related to ongoing pain. Two weeks after L5/6 spinal nerve ligation, deep dorsal horn neurones were recorded in halothane-anesthetized rats. The majority of neurones in neuropathic rats showed increased levels of spontaneous firing with irregular firing patterns. We examined and compared the effects of 5 centrally acting pharmacological agents: morphine (i.t. or i.v.), gabapentin, ketamine, memantine and mepyramine on stimulus-independent neuronal firing. This ongoing activity showed high sensitivity to gabapentin (s.c.) and morphine (i.t.) administration, being significantly reduced in a dose-dependent manner. Morphine administered via the systemic route produced modest but non-significant reductions of spontaneous activity. The two NMDA receptor antagonists, ketamine and memantine, and the histamine H1 receptor antagonist, mepyramine, produced minor effects at doses known to be effective on stimulus evoked measures of deep dorsal horn neurones. This may form an electrophysiological basis for the efficacy of gabapentin and spinal morphine on ongoing pain in patients with peripheral neuropathy.

Authors+Show Affiliations

Department of Pharmacology, Medical Sciences Building, University College London, Gower Street, London WC1E 6BT, UK. ucklrsu@ucl.ac.ukNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16336968

Citation

Suzuki, Rie, and Anthony H. Dickenson. "Differential Pharmacological Modulation of the Spontaneous Stimulus-independent Activity in the Rat Spinal Cord Following Peripheral Nerve Injury." Experimental Neurology, vol. 198, no. 1, 2006, pp. 72-80.
Suzuki R, Dickenson AH. Differential pharmacological modulation of the spontaneous stimulus-independent activity in the rat spinal cord following peripheral nerve injury. Exp Neurol. 2006;198(1):72-80.
Suzuki, R., & Dickenson, A. H. (2006). Differential pharmacological modulation of the spontaneous stimulus-independent activity in the rat spinal cord following peripheral nerve injury. Experimental Neurology, 198(1), 72-80.
Suzuki R, Dickenson AH. Differential Pharmacological Modulation of the Spontaneous Stimulus-independent Activity in the Rat Spinal Cord Following Peripheral Nerve Injury. Exp Neurol. 2006;198(1):72-80. PubMed PMID: 16336968.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential pharmacological modulation of the spontaneous stimulus-independent activity in the rat spinal cord following peripheral nerve injury. AU - Suzuki,Rie, AU - Dickenson,Anthony H, Y1 - 2005/12/05/ PY - 2005/07/20/received PY - 2005/10/07/revised PY - 2005/10/31/accepted PY - 2005/12/13/pubmed PY - 2006/4/28/medline PY - 2005/12/13/entrez SP - 72 EP - 80 JF - Experimental neurology JO - Exp Neurol VL - 198 IS - 1 N2 - Peripheral nerve injury is a significant clinical problem that is often difficult to treat. The major clinical symptoms are numbness, tactile and cooling allodynia, hyperalgesias as well as ongoing pain. In animal models of neuropathy, abnormal responses to applied (or evoked) stimuli can be gauged, but spontaneous pain, a major clinical issue, has proved very difficult to assess. In neuropathic animals, spinal neuronal hyperexcitability indicative of peripheral and central changes with high levels of spontaneous neuronal firing has been reported. This latter stimulus-independent firing of sensory neurones may be a measure related to ongoing pain. Two weeks after L5/6 spinal nerve ligation, deep dorsal horn neurones were recorded in halothane-anesthetized rats. The majority of neurones in neuropathic rats showed increased levels of spontaneous firing with irregular firing patterns. We examined and compared the effects of 5 centrally acting pharmacological agents: morphine (i.t. or i.v.), gabapentin, ketamine, memantine and mepyramine on stimulus-independent neuronal firing. This ongoing activity showed high sensitivity to gabapentin (s.c.) and morphine (i.t.) administration, being significantly reduced in a dose-dependent manner. Morphine administered via the systemic route produced modest but non-significant reductions of spontaneous activity. The two NMDA receptor antagonists, ketamine and memantine, and the histamine H1 receptor antagonist, mepyramine, produced minor effects at doses known to be effective on stimulus evoked measures of deep dorsal horn neurones. This may form an electrophysiological basis for the efficacy of gabapentin and spinal morphine on ongoing pain in patients with peripheral neuropathy. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/16336968/Differential_pharmacological_modulation_of_the_spontaneous_stimulus_independent_activity_in_the_rat_spinal_cord_following_peripheral_nerve_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(05)00407-3 DB - PRIME DP - Unbound Medicine ER -