Discoespondilite Canina : Estudo Retrospectivo de 10 Casos Clínicos

A discoespondilite é uma doença infecciosa rara que afecta, de forma crónica, os discos intervertebrais e as extremidades adjacentes dos corpos vertebrais. Geralmente advém de uma infecção disseminada por via hematógena e os agentes mais frequentes são bacterianos e são principalmente Staphylococcus spp., Streptococcus spp., E. Coli e Brucella spp. Também pode ser devida a infecções fúngicas, parasitárias ou migração de corpos estranhos. É caracterizada pela degenerescência do disco intervertebral e lesões escleróticas e proliferativas das extremidades dos corpos vertebrais. O principal sinal clínico desta doença é a hiperestesia paravertebral e alterações da marcha ou relutância ao movimento. Febre e anorexia são menos frequentes do que seria de esperar e os sinais neurológicos são considerados raros. O diagnóstico desta doença é geralmente radiográfico e a determinação do agente pode ser conseguida por cultura de material discal, hemocultura ou urocultura. Podem ser usados meios de imagiologia avançada como TAC e RM para melhor avaliar a extensão das lesões e o envolvimento dos tecidos circunvizinhos. A realização de hemogramas raramente revela alterações significativas embora possa existir leucocitose. O tratamento médico é eficaz em aproximadamente 76% dos casos e deve ser feito com base em cultura e TSA mas, de forma empírica, as cefalosporinas de primeira geração são frequentemente utilizadas. Em alguns casos pode ser necessária a estabilização ou desbridamento cirúrgicos. O estudo retrospectivo realizado no âmbito deste trabalho, teve como objectivo avaliar os sinais clínicos, radiográficos e laboratoriais , assim como o maneio médico e cirúrgico de 10 casos de discoespondilite confirmada radiográfica e clinicamente, num período de 2 anos. Observou-se maior prevalência da doença em machos, em cães jovens e adultos, e raças de grande porte. A região mais afectada foi a junção lombossagrada, e o sinal mais observado foi a dor paraespinhal. No entanto os sinais neurológicos foram mais frequentes do que o descrito. Os agentes isolados em cultura de material discal não foram os mais comuns. O tratamento médico instituído pelos veterinários foi eficaz em 6 dos casos, Foi necessária intervenção cirúrgica em 3 e 1 animal não recuperou totalmente até à conclusão deste estudo.

Symptoms of imbalance associated with cervical spine pathology

The goals of the present study are: to determine the prevalence of dizziness or imbalance in a population of patients with cervical-spine pathology as compared to that in the general population; to determine correlations between cervical spinal pathology and symptoms of dizziness or imbalance.

Perceived controllability modulates the neural response to pain

The response to painful stimulation depends not only on peripheral nociceptive input but also on the cognitive and affective context in which pain occurs. One contextual variable that affects the neural and behavioral response to nociceptive stimulation is the degree to which pain is perceived to be controllable. Previous studies indicate that perceived controllability affects pain tolerance, learning and motivation, and the ability to cope with intractable pain, suggesting that it has profound effects on neural pain processing. To date, however, no neuroimaging studies have assessed these effects. We manipulated the subjects' belief that they had control over a nociceptive stimulus, while the stimulus itself was held constant. Using functional magnetic resonance imaging, we found that pain that was perceived to be controllable resulted in attenuated activation in the three neural areas most consistently linked with pain processing: the anterior cingulate, insular, and secondary somatosensory cortices. This suggests that activation at these sites is modulated by cognitive variables, such as perceived controllability, and that pain imaging studies may therefore overestimate the degree to which these responses are stimulus driven and generalizable across cognitive contexts. [References: 28]

Individual differences in the effects of perceived controllability on pain perception: critical role of the prefrontal cortex

The degree to which perceived controllability alters the way a stressor is experienced varies greatly among individuals. We used functional magnetic resonance imaging to examine the neural activation associated with individual differences in the impact of perceived controllability on self-reported pain perception. Subjects with greater activation in response to uncontrollable (UC) rather than controllable (C) pain in the pregenual anterior cingulate cortex (pACC), periaqueductal gray (PAG), and posterior insula/SII reported higher levels of pain during the UC versus C conditions. Conversely, subjects with greater activation in the ventral lateral prefrontal cortex (VLPFC) in anticipation of pain in the UC versus C conditions reported less pain in response to UC versus C pain. Activation in the VLPFC was significantly correlated with the acceptance and denial subscales of the COPE inventory [Carver, C. S., Scheier, M. F., & Weintraub, J. K. Assessing coping strategies: A theoretically based approach. Journal of Personality and Social Psychology, 56, 267–283, 1989], supporting the interpretation that this anticipatory activation was associated with an attempt to cope with the emotional impact of uncontrollable pain. A regression model containing the two prefrontal clusters (VLPFC and pACC) predicted 64% of the variance in pain rating difference, with activation in the two additional regions (PAG and insula/SII) predicting almost no additional variance. In addition to supporting the conclusion that the impact of perceived controllability on pain perception varies highly between individuals, these findings suggest that these effects are primarily top-down, driven by processes in regions of the prefrontal cortex previously associated with cognitive modulation of pain and emotion regulation.

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to he stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase H and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright (C) 2008 John Wiley & Sons, Ltd.

The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain

Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include allodynia (touch-evoked pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in voltage-dependent calcium channel (VDCC) expression and function; however, the role of Ca(v)2.3 calcium channels has not clearly been defined. Here, the effects of SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve ligation (SNL) model of chronic neuropathic pain [Kim & Chung, (1992) Pain, 50, 355-363] was used to induce mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to sham-operated animals. Spinal SNX-482 (0.5-4 mu g/50 mu L) exerted dose-related inhibitions of noxious C-fibre- and A delta-fibre-mediated neuronal responses in conditions of neuropathy, but not in sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to SNX-482. In contrast, non-noxious A beta-mediated responses were not affected by SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3 calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage.