. Author manuscript; available in PMC: 2009 Dec 14.

Published in final edited form as: Curr Pain Headache Rep. 2009 Jun;13(3):208–214. doi: 10.1007/s11916-009-0035-8

Table 1. Modification of endogenous inhibitory mechanisms in the spinal cord after nerve injury.

NPP = Neuropathic Pain. TMP = thiamine monophosphatase, which generates the inhibitory neurotransmitter, adenosine. Receptor down-regulation could induce loss of opioid sensitivity. Conversely, noradrenergic sprouting, enhanced α₂ receptor-G protein coupling, and de novo CB2 expression could explain the enhanced efficacy of duloxetine, clonidine, and cannabinoids as analgesics for neuropathic pain, respectively.

Mechanism	Recent Example	Proposed Impact on NPP
Receptor down-regulation	Mu-opioid	unimpeded
Enzyme down-regulation	TMP [43]	unimpeded
Reversal of chloride channel	GABA_A	unimpeded
Sprouting of nerve endings	noradrenergic [29]	constrained
Receptor-G protein coupling	α₂ receptor [30]	constrained
de novo expression in microglia	CB2 receptor	constrained
Neurotransmitter up-regulation	Neuropeptide Y	constrained
Receptor up-regulation	M2 receptors	constrained