Pain Inhibiting Circuits – Neuropathic Pain – Good Gone Bad?

Your body has a set of circuits to shut off pain – your endophin circuits, except in the spinal cord the endophins are called “enkaphalins” and are chemically built a bit different.¬† The pain inhibiting spinal circuits i.e. the “descending pain modulatory pathway” go from the brainstem rostral ventromedial medulla (RVM) via the dorsolateral funiculus (DLF).¬† Now it appears cells in this RVM can either prevent or facilitate pain.

Brain. 2008 Dec 2. [Epub ahead of print]
Neuropathic pain is maintained by brainstem neurons co-expressing opioid and cholecystokinin receptors. Zhang W, Gardell S, Zhang D, Xie JY, Agnes RS, Badghisi H, Hruby VJ, Rance N, Ossipov MH, Vanderah TW, Porreca F, Lai J. abstract

  • In the spinal RVM, there are pain related cells and 80% of them have both morphine receptors (mu opioid) and CCK receptors. CCK was originally thought to be a gut hormone but now appears to have important pain transmission roles.
  • microinjection of CCK into the RVM causes pain
  • lesions of the RVM circuit will prevent neuropathic pain from a severed nerve lasting more than 9 days.

There has been prior evidence the pain inhibitor circuits can do the opposite:

Brain Res Brain Res Rev. 2004 Nov;46(3):295-309.
Descending control of persistent pain: inhibitory or facilitatory? Vanegas H, Schaible HG abstract 

In another recent study, blocking the descending circuits at the medullary(brain stem level) dorsal reticular nucleus attenuated pain as well.

Brain Res. 2008 Jan 10;1188:69-75.
Contribution by DRt descending facilitatory pathways to maintenance of spinal neuron sensitization in rats.Sotgiu ML, Valente M, Storchi R, Caramenti G, Mario Biella GE abstract

Comment – I always thought that the spinal cord is where much of the action in neuropathic pain occurs. Will we see a new generation of CCK inhibitors on the horizon? michael kors handtasche sale michael kors handtasche sale

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