Andres M. Lozano
James W. Leiphart and Frank H. Valone III
The use of deep brain stimulation (DBS) has recently been expanded to the investigational treatment of specific psychiatric disorders. Much like movement disorders, the targets selected for DBS are based on past experience with stereotactic lesions. A literature review of past studies incorporating stereotactic lesions for psychiatric disorders was performed to provide historical context and possible guidance for current and future attempts at treating psychiatric disorders with DBS.
Original copies of the proceedings of the second, third, fourth, and fifth World Congresses of Psychiatric Surgery meetings were reviewed, and a Medline search was conducted for studies with the word “psychosurgery” and each of 14 highly prevalent psychiatric conditions identified by the National Institute of Mental Health. Postoperative results for 1145 patients with stereotactic brain lesions targeting various anatomical foci were standardized using a 5-point scale (3 [free of symptoms] to −1 [worse]). Each patient was entered into a database as a unique data point and used for this literature review.
General anxiety disorder and obsessive-compulsive disorder had the greatest reported improvements from anterior capsulotomy, and bipolar disorder, depression, and schizoaffective disorder had the greatest reported improvements from anterior cingulotomy, supporting these areas for DBS investigation. Addiction and schizophrenia showed the least improvement from surgery. Therefore, pursuing the treatment of these disorders with DBS using the targets in these studies may be ineffective.
This study provides retrospective data that suggest which anatomical focus may be effective to lesion or stimulate for the treatment of each of several psychiatric disorders.
James W. Leiphart, Cynthia V. Dills and Robert M. Levy
Object. Intrathecally administered α2-adrenergic receptor subtype—specific antagonists were used to determine which α2-adrenergic receptor subtype mediates the analgesic effect of intrathecally administered tizanidine in a chronic constriction injury (CCI) rat model of neuropathic pain.
Methods. Seven days after CCI and intrathecal catheter surgeries had been performed in Sprague—Dawley rats, baseline neuropathic pain tests including cold-floor ambulation and paw pinch were performed. Either the dimethyl sulfoxide vehicle (seven rats) or one of the antagonists—5, 23, or 46 µg yohimbine (22 rats); 5, 25, 50, or 100 µg prazosin (25 rats); or 5, 45, or 90 µg WB4101 (11 rats)—were intrathecally administered to the animals, followed in 30 minutes by 50 µg intrathecally administered tizanidine. The neuropathic pain tests were repeated 30 minutes later. The resulting profile showed a descending order of antagonist efficacy for yohimbine, prazosin, and WB4101 for the cold-floor ambulation test and for the paw-pinch test of the affected paw. As expected given tizanidine's lack of analgesic effect on the contralateral, normal paw, there were no effects of antagonists on contralateral paw responses. The results of the paw-pinch test on the affected side were compared with binding data cited in the existing literature for the three different α2-adrenergic receptor subtypes (α2A, α2B, and α2C) with yohimbine, prazosin, and WB4101. The antagonist response profile for the paw-pinch test of the affected paw most closely approximated the α2B receptor binding profile.
Conclusions. The antagonist profile from the current study is most consistent with the theory that the α2B-adrenergic receptor subtype mediates the analgesic effect of intrathecally administered tizanidine on CCI-associated neuropathic pain.
James W. Leiphart, Cynthia V. Dills, Ofer M. Zikel, Daniel L. Kim and Robert M. Levy
✓ The antinociceptive actions of morphine and tizanidine (an α2-adrenergic agonist) administered intrathecally in a rat model of mononeuropathic pain were investigated. Tizanidine increased to normal levels the intensity of a noxious pressure stimulus required to induce paw withdrawal (p < 0.01) and decreased the duration of limb withdrawal from both normal-temperature and cooled floors in a dose-dependent manner (p < 0.01). Tizanidine had virtually no effect on the latency of paw withdrawal from a noxious heat stimulus. In comparison, morphine significantly decreased, in a dose-dependent manner, limb withdrawal from the normal-temperature and cooled floors and increased to cutoff values the withdrawal latencies of both noxious heat and pressure stimuli (p < 0.01). The effect of tizanidine was limited to the hyperalgesic limb and served to normalize reactive latencies, whereas morphine affected both hindlimbs and increased latencies to supranormal cutoff values. These data suggest that intrathecal tizanidine may be more specific than morphine in reversing the allodynia and hyperpathia associated with neuropathic pain states and may be of value in the management of patients with these clinical syndromes.
James W. Leiphart, Prasanna P. Vasudevan, Samer R. Rajjoub, Luis W. Dominguez and Jason Chang
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.
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.
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.
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 patient's nutrition.