• Pain · Nov 2006

    Tonic inhibitory role of alpha4beta2 subtype of nicotinic acetylcholine receptors on nociceptive transmission in the spinal cord in mice.

    • Md Harunor Rashid, Hidemasa Furue, Megumu Yoshimura, and Hiroshi Ueda.
    • Department of Integrative Physiology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan. mdharunor.rashid@mcgill.ca
    • Pain. 2006 Nov 1;125(1-2):125-35.

    AbstractIn the spinal dorsal horn, activation of the nicotinic acetylcholine receptors (nAChR) by exogenously applied agonists is known to enhance inhibitory synaptic transmission, and to produce analgesia. However, it is still unknown whether endogenously released acetylcholine exerts a tonic inhibition on nociceptive transmission through the nAChRs in the spinal dorsal horn. Here, we report the presence of such a tonic inhibitory mechanism in the spinal dorsal horn in mice. In behavioral experiments, intrathecal (i.t.) injection of non-selective nAChR antagonist mecamylamine and alpha4beta2 subtype-selective antagonist dihydro-beta-erythroidine (DHbetaE) dose-dependently induced thermal and mechanical hyperalgesia in mice while the alpha7-selective antagonist methyllycaconitine (MLA) had no effect. Similarly, antisense knock-down of alpha4 subunit of nAChR, but not alpha7 subunit, in spinal cord induced thermal and mechanical hyperalgesia. In whole-cell patch-clamp experiments in spinal cord slice preparation from adult mice, the frequency of miniature inhibitory postsynaptic currents (mIPSCs) observed in substantia gelatinosa (SG) neurons was decreased by mecamylamine and DHbetaE, but not by MLA. The amplitudes of the mIPSCs were not affected. The nicotinic antagonists decreased the frequency of both GABAergic and glycinergic IPSCs. On the other hand, the nicotinic antagonists had no effect on the excitatory postsynaptic currents (EPSCs). Finally, acetylcholine-esterase inhibitor neostigmine-induced facilitation of IPSC frequencies in SG neurons was inhibited by mecamylamine and DHbetaE. Altogether these findings suggest that nicotinic cholinergic system in the spinal dorsal horn can tonically inhibit nociceptive transmission through presynaptic facilitation of inhibitory neurotransmission in SG via the alpha4beta2 subtype of nAChR.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…