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The development of thermal allodynia in relationship to sodium channel augmentation in dorsal root ganglia (DRGs) was studied in albino rats. Paw withdrawal latencies were measured hourly following complete Freund's adjuvant (CFA) injections. Sodium channels were demonstrated with immunocytochemistry. Sustained minimum latencies were attained between 10 and 12 h post-injection. Sodium channel labeling began to increase at 23 h post-injection and reached maximum levels by 24 h. Thermal hypersensitivity is thus established 12 h before sodium channel augmentation can be demonstrated.

The mechanisms by which inflammation induces a chronic pain state are poorly understood. Following the induction of many painful conditions, an increase in the spontaneous firing rate of neurons is often observed in peripheral sensory ganglia. Since ion channels are essential mediators of spike generation and impulse conduction, it is reasonable to postulate that local changes in ion channel expression might underlie the changes in membrane excitability. Such alterations may serve to enhance the efficiency by which painful stimuli are transduced and then conducted to the central nervous system. In these studies, we employed immunocytochemical methods to investigate the changes in sodium channel expression in dorsal root ganglia of rats following a subcutaneous injection of complete Freund's adjuvant, an inducer of chronic inflammation. We find that sodium channel immunoreactivity within primary sensory neurons is dramatically increased within 24 h of the complete Freund's adjuvant injection. These changes persist in small neurons for at least 2 months and roughly parallel the time course of behaviorally measured changes in pain thresholds. Thus, the regulation of sodium channel synthesis may play a role in the generation and maintenance of the hyperesthetic state seen in chronic inflammation.

Ranolazine modulates the cardiac voltage-gated sodium channel (NaV 1.5) and is approved by the FDA in the treatment of ischemic heart disease. Ranolazine also targets neuronal (NaV 1.7, 1.8) isoforms that are implicated in neuropathic pain. Therefore, we determined the analgesic efficacy of ranolazine in a preclinical animal model of neuropathic pain. Both intraperitoneal and oral administration of ranolazine dose-dependently inhibited the mechanical and cold allodynia associated with spared nerve injury, without producing ataxia or other behavioral side effects. These data warrant clinical investigation of the potential use of ranolazine in the treatment of neuropathic pain.

The results of this study demonstrate the existence of single neocortical neurons that send axon collaterals into the corpus callosum, to terminate within the contralateral hemisphere, and subcortically, to terminate within the ipsilateral superior colliculus.

A new technique is described that minimizes the damage to neural tissues caused by the cortical incisions that must be made when operating on intracerebral or intraventricular lesions. Symmetric cortical incisions were made bilaterally in the same region of the middle suprasylvian gyrus in six dogs. Blunt dissection was performed on the right side. A new technique, which utilizes a balloon catheter, was employed on the left side. A greater hemiparesis was observed on the left side in all dogs. There was a mild but definite hemiparesis on the right side in four dogs, which improved within 2–3 days postoperatively. The dogs were killed on the sixth postoperative day. The Fink-Heimer technique for selective staining of degenerating axons and their terminal boutons was used to determine the extent of neuronal damage. Histologic studies support clinical observations in the experimental animal that the neural damage resulting from cortical incision is significantly decreased when the balloon catheter technique is applied.