From: Subject: d-cycloserine reduces neuropathic pain behavior through limbic NMDA-mediated circuitry Date: Tue, 1 Apr 2008 17:47:04 -0500 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0165_01C89420.659A3B50" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3198 This is a multi-part message in MIME format. ------=_NextPart_000_0165_01C89420.659A3B50 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.chronicfatiguesyndromesupport.com/library/showarticle.cfm?ID=8235 =EF=BB=BF d-cycloserine reduces neuropathic pain behavior = through limbic NMDA-mediated circuitry
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d-cycloserine reduces neuropathic = pain=20 behavior through limbic NMDA-mediated circuitry=20
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d-cycloserine = reduces=20 neuropathic pain behavior through limbic = NMDA-mediated=20 circuitry


by M = Millecamps and=20 AV Apkarian, et=20 al.
ChronicFatigue.com

08-11-2007

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[Note:=20 Neuropathic pain is pain owing to a = malfunctioning=20 nervous system. D-cycloserine is an antibiotic=20 prescribed for tuberculosis that has shown = promise in=20 studies as a means of reducing conditioned fear = - such=20 as social anxiety - by assisting brain chemicals = at the=20 glutamatergic N-methyl-D-aspartate (NMDA) = receptor,=20 which plays an important role in learning and=20 memory.]=20

Human brain imaging studies suggest that = chronic=20 neuropathic pain has a strong emotional = component that=20 is mediated by medial prefrontal cortex (mPFC) = activity;=20 in rodents, the mPFC is involved in emotional = and=20 cognitive aspects of behavior, including the = extinction=20 of Pavlovian fear conditioning.=20

Together, these findings suggest that the = cortex may=20 modulate the memory trace of pain.=20

As d-cycloserine (DCS), a partial agonist of = the NMDA=20 receptor, can enhance learning and potentiate = the=20 extinction of acquired fear, in the present = study we=20 tested its efficacy in neuropathic pain = behavior.=20

In rats with spared nerve injury (SNI), = repeated=20 daily oral administration of DCS reduced = mechanical=20 sensitivity of the injured limb in a = dose-dependent=20 manner; this effect continued for weeks after = the=20 cessation of DCS treatment.=20

In addition, re-exposure to DCS further = enhanced=20 antinociceptive behavior. Repeated oral DCS=20 administration also reduced cancer chemotherapy=20 drug-induced neuropathic pain behavior. = Infusions of DCS=20 directly into the mPFC (especially within = prelimbic=20 cortex) or the amygdala (but not into thalamus, = insula,=20 or occipital cortex) acutely induced = antinociception in=20 SNI rats. The antinociceptive effect of = intra-mPFC DCS=20 infusions was mimicked by NMDA and glycine, and = blocked=20 by HA 966. In the mPFC of SNI rats, NR2B = expression was=20 down-regulated; however, this effect was = reversed with=20 repeated oral DCS.=20

Lastly, infusions of DCS into mPFC reversed = place=20 avoidance behavior induced by mechanical = stimulation of=20 the injured paw in SNI rats.=20

These findings indicate that limbic = NMDA-mediated=20 circuitry is involved in long-term reduction in=20 neuropathic pain behavior.=20

Source: Pain. 2007 Apr 19; [E-publication = ahead of=20 print] PMID: 17449176, by Millecamps M, Centeno = MV,=20 Berra HH, Rudick CN, Lavarello S, Tkatch T, = Apkarian AV.=20 Department of Physiology, Feinberg School of = Medicine,=20 Northwestern University, Chicago, Illinois, USA. = [E-mail: a-apkarian@northwestern.edu]=20

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