An investigation into the inhibitory function of serotonin in diffuse noxious inhibitory controls in the neuropathic rat

被引:55
作者
Bannister, K. [1 ]
Lockwood, S. [1 ]
Goncalves, L. [1 ]
Patel, R. [1 ]
Dickenson, A. H. [1 ]
机构
[1] UCL, Dept Neurosci, Physiol & Pharmacol, London WC1E 6BT, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
CONDITIONED PAIN MODULATION; DORSAL-HORN NEURONS; PERIPHERAL-NERVE INJURY; SPINAL-CORD; BEHAVIORAL HYPERSENSITIVITY; SELECTIVE INHIBITOR; CONVERGENT NEURONS; 5-HT3; RECEPTORS; LILLY; 110140; INVOLVEMENT;
D O I
10.1002/ejp.979
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background: Following neuropathy alpha 2-adrenoceptor-mediated diffuse noxious inhibitory controls (DNIC), whereby a noxious conditioning stimulus inhibits the activity of spinal wide dynamic range (WDR) neurons, are abolished, and spinal 5-HT7 receptor densities are increased. Here, we manipulate spinal 5-HT content in spinal nerve ligated (SNL) animals and investigate which 5-HT receptor mediated actions predominate. Methods: Using in vivo electrophysiology we recorded WDR neuronal responses to von frey filaments applied to the hind paw before, and concurrent to, a noxious ear pinch (the conditioning stimulus) in isoflurane-anaesthetised rats. The expression of DNIC was quantified as a reduction in WDR neuronal firing in the presence of conditioning stimulus and was investigated in SNL rats following spinal application of (1) selective serotonin reuptake inhibitors (SSRIs) citalopram or fluoxetine, or dual application of (2) SSRI plus 5-HT7 receptor antagonist SB269970, or (3) SSRI plus alpha 2 adrenoceptor antagonist atipamezole. Results: DNIC were revealed in SNL animals following spinal application of SSRI, but this effect was abolished upon joint application of SSRI plus SB269970 or atipamezole. Conclusions: We propose that in SNL animals the inhibitory actions (quantified as the presence of DNIC) of excess spinal 5-HT (presumed present following application of SSRI) were mediated via 5-HT7 receptors. The anti-nociception depends upon an underlying tonic noradrenergic inhibitory tone via the alpha 2-adrenoceptor. Significance: Following neuropathy enhanced spinal serotonin availability switches the predominant spinal 5-HT receptor-mediated actions but also alters noradrenergic signalling. We highlight the therapeutic complexity of SSRIs and monoamine modulators for the treatment of neuropathic pain.
引用
收藏
页码:750 / 760
页数:11
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