Intrathecal administration of a gap junction decoupler, an inhibitor of Na(+)-K(+)-2Cl(-) cotransporter 1, or a GABA(A) receptor agonist attenuates mechanical pain hypersensitivity induced by REM sleep deprivation in the rat.
We studied the hypothesis that some of the spinal mechanisms that are involved in neuropathic hypersensitivity play a role in hypersensitivity induced by REM sleep deprivation (REMSD). Rats with a chronic intrathecal (i.t.) catheter had REMSD of 48h duration that induced hypersensitivity to mechanical stimulation. After REMSD, the animals were treated i.t. with carbenoxolone (a gap junction decoupler), bumetanide (a blocker of Na(+)-K(+)-2Cl(-) cotransporter 1 or NKCC1), muscimol (a GABA(A) receptor agonist), or pretreated intraperitoneally with minocycline (an inhibitor of microglia activation). Previously, all these treatments attenuated neuropathic hypersensitivity. Following REMSD, carbenoxolone, bumetanide and muscimol had a strong antihypersensitivity effect, whereas pretreatment with minocycline failed to prevent development of hypersensitivity. The results suggest that among spinal pain facilitatory mechanisms that are common to REMSD and neuropathy are NKCC1 blocker- and gap junction decoupler-reversible mechanisms. Moreover, there is a net pain inhibitory effect by spinal administration of an exogenous GABA(A) receptor agonist following REMSD as shown earlier in neuropathy. In contrast, activation of spinal microglia may not be as important for the development of hypersensitivity induced by REMSD as following nerve injury.
Wei
Hong
H
King's Lab, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, PR China.
Hao
Bin
B
Huang
Jin-Lu
JL
Ma
Ai-Niu
AN
Li
Xin-Yan
XY
Wang
Yong-Xiang
YX
Pertovaara
Antti
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects; D018755:GABA Agonists / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects*; D006930:Hyperalgesia / Q000517:prevention & control* / Q000523:psychology; D007278:Injections, Spinal; D017628:Microglia / Q000187:drug effects; D008845:Microinjections; D008911:Minocycline / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D012892:Sleep Deprivation / Q000523:psychology*; D028021:Sodium-Potassium-Chloride Symporters / Q000187:drug effects / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2
D018118:Chloride Channels; D018755:GABA Agonists; D011963:Receptors, GABA-A; C578879:Slc12a2 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D009118:Muscimol; D008911:Minocycline; D002229:Carbenoxolone