[EXPERIMENTAL MODELS OF ALCOHOLIC NEUROPATHY IN RATS.]

The aim of this work was to study the behavioral and histopathomorphological signs of peripheral neuropathy development in male Wistar rats on the model of alcoholic neuropathy. Chronic consumption of ethanol solution with concentration increasing from 7.47 to 26.2% (w/w) resulted in neuropathy (allodynia) de- velopment after 8 weeks of chronic alcohol administration. The behavioral signs of allodynia became significant on the 8th week and were retained up to the end of experiment (15 weeks of ethanol administration). The reference drug gabapentin effectively reduced the manifestation of allodinia. Histological exami- nation of sciatic nerve preparations from animals killed after ethanol consumption for 5, 10 and 15 weeks revealed the development of histopathomorphological pattern with increasing duration of chronic alcoholization. At the initial stage, the morphological basis of observed behavioral manifestations was provided by excess lipid deposition in peri/epineurium of nerve specimens). The further increase in treatment duration (up to 10 and 15 weeks) was associated with demye- lination and development of inflammation of the sciatic nerve. This experimental model allows one to investigate the efficacy of new neuroprotective and ana- lgesic substances - potential drugs for both prevention and management of neuropathy.

Independent contributions of alcohol and stress axis hormones to painful peripheral neuropathy.

Painful small-fiber peripheral neuropathy is a debilitating complication of chronic alcohol abuse. Evidence from previous studies suggests that neuroendocrine mechanisms, in combination with other, as yet unidentified actions of alcohol, are required to produce this neuropathic pain syndrome. In addition to neurotoxic effects of alcohol, in the setting of alcohol abuse neuroendocrine stress axes release glucocorticoids and catecholamines. Since receptors for these stress hormones are located on nociceptors, at which they can act to cause neuronal dysfunction, we tested the hypothesis that alcohol and stress hormones act on the nociceptor, independently, to produce neuropathic pain. We used a rat model, which allows the distinction of the effects of alcohol from those produced by neuroendocrine stress axis mediators. We now demonstrate that topical application of alcohol and exposure to unpredictable sound stress, each alone, has no effect on the nociceptive threshold. However, when animals that had previous exposure to alcohol were subsequently exposed to stress, they rapidly developed mechanical hyperalgesia. Conversely, sound stress followed by topical alcohol exposure also produced mechanical hyperalgesia. The contribution of stress hormones was prevented by spinal intrathecal administration of oligodeoxynucleotides antisense to ß(2)-adrenergic or glucocorticoid receptor mRNA, which attenuates receptor level in nociceptors, as well as by adrenal medullectomy. These experiments establish an independent role of alcohol and stress hormones on the primary afferent nociceptor in the induction of painful peripheral neuropathy.

[Neuropathic pain syndrome: clinico-neurophysiological analysis]. / Nevropaticheskii bolevoi sindrom: kliniko-neirofiziologicheskii analiz.

Neurophysiological study of all links of afferent somatosensory systems in neuropathies of different genesis was conducted. Patients with alcoholic (APN) and diabetic (DNP) polyneuropathies have been examined and selected as follows: 19 patients with intensive spontaneous pain syndrome (scoring over 6 on VAS); 20--without pain; 22 patients with allodiny caused by neuropathic pain and 38--without allodiny. Control group included 20 healthy subjects. Symptom complex of pain syndrome encompassed pronounced disorders of cutaneous sensitivity, minus symptoms in deep sensory sphere and high depression level. Neurophisiological appearances of spontaneous pain syndrome in APN and DPN are characterized by generalized mixed damage of peripheral sensible nerves and of 1 beta-afferents of H-reflex arch. Insufficiency of function of pain control system was mainly of deafferent character. Allodiny and spontaneous pain syndrome are reciprocally combined, the former being distinguished by involvement in pathology of 1-[symbol: see text] fibers (motor nerves and efferent links of H-reflex).

Neurocognitive impairment associated with alcohol use disorders: implications for treatment.

Between 50% and 80% of individuals with alcohol use disorders experience mild to severe neurocognitive impairment. There is a strong clinical rationale that neurocognitive impairment is an important source of individual difference affecting many aspects of addiction treatment, but empirical tests of the direct influence of impairment on treatment outcome have yielded weak and inconsistent results. The authors address the schism between applied-theoretical perspectives and research evidence by suggesting alternative conceptual models of the relationship between neurocognitive impairment and addiction treatment outcome. Methods to promote neurocognitive recovery and ways in which addiction treatments may be modified to improve psychosocial adaptation are suggested. Specific suggestions for future research that may help clarify the complex relations between neurocognitive impairment and addiction treatment are outlined.