James W. Leiphart

Two‐year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial

To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci.

Event-related potential correlates of implicit priming and explicit memory tasks

The difference between implicit and explicit memory was examined using event-related potentials (ERP). 16 college students read a study list of 100 words (50 high-emotion and 50 low-emotion) from a video monitor. They then performed a perceptual identification (P.I.) task in which they attempted to identify each of a series of 100 words (including 50 from the study list) presented at recognition threshold. Finally, the subjects performed a yes-no recognition task in which they were presented with the other 50 words from the first list and 50 new words (suprathreshold), and they had to identify which ones had been seen in the study list. Subjects were more likely to identify studied than nonstudied words in the perceptual identification task; there was no effect of emotion. In the yes-no recognition task, more high than low-emotion words were responded to correctly for the old words, whereas more low than high-emotion words were responded to correctly for the new words. Data from 11 of the subjects contained enough artifact-free trials for ERP analysis. Analysis revealed that in both the perceptual identification task and the yes-no recognition task, P3 amplitude was larger for old than new words, and emotionality had no effect. Analysis of ERPs in the perceptual identification task averaged according to behavioral response, as well as according to prior study effect showed that P3 amplitude was larger for the studied words than non-studied words, regardless of behavioral response. This effect is electrophysiological evidence that a specific event occurs in the brain in response to the presentation of studied words, whether or not those words are consciously perceived. P3 latency differed as a function of previous study in the yes-no task but not the perceptual identification task.

Analgesic Action of Acute and Chronic Intraspinally Administered Opiate and α2-Adrenergic Agonists in Chronic Neuropathic Pain

Intrathecal (IT) administration of opiate analgesics has become a popular method of pain control in patients with pain of both malignant and nonmalignant origin. Therapeutic efficacy for nonmalignant pain states might be improved by having a broader range of available pharmacologic agents for intrathecal administration. Toward this aim, we have applied a new model of neuropathic pain in the rat to evaluate the relative analgesic efficacy and potential cross tolerance of both acutely and chronically administered IT morphine (MS) and tizanidine (TZ), an alpha 2-adrenergic agonist. Under anesthesia, 225 Sprague-Dawley male rats underwent unilateral multiple partial suture ligation of the sciatic nerve. This produces a syndrome similar to human neuropathic pain. Chronic lumbar IT cannulae were placed via the cisterna magna. Seven days after surgery, animals were tested for spontaneous ambulation and paw pinch tolerance. These tests correlate with human clinical observations of chronic pain and hyperpathia. For the acute drug administration, animals were then given saline, 10, 20, or 30 micrograms IT MS or 10, 25 or 50 micrograms IT TZ and testing was repeated. Preliminary results suggest that MS, in a dose-dependent manner, significantly decreased abnormal limb withdrawal from the floor while ambulating and increased paw pinch withdrawal latency to cutoff values (p < or = 0.01 in all tests). IT MS had significant effects on pain sensation in the operated and unoperated limbs, increasing latencies to cutoff and nonspecifically inhibiting pain transmission. IT TZ had a similar effect on decreasing limb withdrawal from the floor, but paw pinch withdrawal latency was increased only to the normal range, not to cutoff values. These effects were also dose-dependent. For chronic drug administration, after baseline testing, osmotic minipumps (Alza, Palo Alto, Calif.) delivering either saline, 60 or 120 micrograms/day MS, or 75 or 150 micrograms/day TZ were attached to the IT catheter. Testing was done on days 1, 4, 7 and 14 after pump attachment. On day 14, the animals were given an IT bolus of the noninfused drug (50 micrograms tizanidine or 30 micrograms morphine) and the tests were repeated to determine degree of cross tolerance. Initially, chronic MS and TZ administration produced a similar degree of analgesia seen with results obtained with acute administration. The animals rapidly became tolerant to these agents so that by day 4, neither drug had an analgesic effect. No significant cross tolerance between MS and TZ was observed. Thus, both IT MS and TZ are analgesic in experimental chronic neuropathic pain.(ABSTRACT TRUNCATED AT 400 WORDS)

The Analgesic Effects of Intrathecally Pumped Saline and Artificial Cerebrospinal Fluid in a Rat Model of Neuropathic Pain.

Objective. This experiment was performed to test the hypothesis that intrathecally pumped saline, but not artificial cerebrospinal fluid (CSF), would be analgesic in a rat model of neuropathic pain.

The effect of acute postoperative pain and chronic neuropathic pain on subsequent weight gain in the rat.

OBJECT Acute postoperative pain has demonstrated effects on appetite and weight gain in human studies. This study was designed to test the hypothesis that chronic neuropathic pain has a more significant effect on weight than acute postsurgical pain. METHODS One hundred eighteen rats were separated into 3 groups: common sciatic nerve ligation, surgery without ligation, and no surgery. Each group was further divided to undergo testing at 3, 7, and 14 days. On the day of testing, the rats were tested for signs of pressure and heat hyperalgesia and were weighed. RESULTS The effect on the percentage of change in body weight from the day of surgery to the day of testing was statistically significant for both the condition (F = 15.0, p < 0.0001) and the day of testing (F = 43.3, p < 0.0001). The rats that received no surgery had a change in weight of 2.3% on Day 3, 4.0% on Day 7, and 10.7% on Day 14. In the nonligation surgery group, the change was -3.8% on Day 3, 2.0% on Day 7, and 9.7% on Day 14. In the ligation surgery group, the change was -6.3% on Day 3, -0.7% on Day 7, and 4.9% on Day 14. This group began gaining weight by Day 14 but continued to have less weight gain than the other groups by Day 14. CONCLUSIONS Neuropathic pain inhibits weight gain more than normal, postsurgical pain. Recognizing the difference and initiating effective treatment for neuropathic pain may have an impact on the patients nutrition.