Descending nociceptive inhibition is modulated in a time-dependent manner in a double-hit model of chronic/tonic pain.

Clinical evidences suggest that an imbalance between descending inhibition and facilitation drives the development of chronic pain. However, potential mechanisms promoting the establishment of a persistent pain state and the increased pain vulnerability remain unknown. This preclinical study was designed to evaluate temporal changes in descending pain modulation at specific experimental endpoints (12, 28, 90 and 168 days) using a novel double-hit model of chronic/tonic pain (first hit: chronic constriction injury (CCI) model; second hit: tonic formalin pain in the contralateral hindpaw). Basal activity of bulbo-spinal monoaminergic systems was further assessed through liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) screening of cerebrospinal fluid (CSF). We found that CCI-operated rats exhibited a reduced nociceptive response profile, peaking on day 28, when subjected to tonic pain. This behavioral response was accompanied by a rapid increase in basal CSF serotonin and norepinephrine levels 12 days after neuropathy, followed by a return to sham levels on day 28. These molecular and behavioral adaptive changes in descending pain inhibition seemed to slowly fade over time. We therefore suggest that chronic neuropathic pain produces a transient hyperactivation of bulbo-spinal monoaminergic drive when previously primed using a tonic pain paradigm (i.e., formalin test), translating into inhibition of subsequent nociceptive behaviors. Altogether, we propose that early hyperactivation of descending pain inhibitory mechanisms, and its potential ensuing exhaustion, could be part of the temporal neurophysiological chain of events favoring chronic neuropathic pain establishment.

Complex chromosomal rearrangement in a mentally retarded boy without gross dysmorphic stigmata.

A boy with severe mental retardation and complex, apparently balanced chromosomal rearrangement (CCR) of autosomes 1, 3 and 5 is described. This complex chromosomal rearrangement involved three translocations and one insertion; five breakpoints were found, at 1p31, 3p22, 3p26, 5p14 and 5q23.

Short stature, craniofacial dysmorphism and dento-skeletal abnormalities in a large kindred. A variant of K.B.G. syndrome or a new mental retardation syndrome.

A possibly new mental retardation syndrome is described in a large family. The major features of the syndrome are: short statue, craniofacial dysmorphism and dento-skeletal abnormalities. The mode of inheritance of this syndrome appears to be autosomal dominant with a variable degree of expressivity. The possible similarity to another autosomally dominant inherited mental retardation syndrome, "the K.B.G. syndrome" as described by Hermann et al. (1975), is discussed.