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Biomedical subjects

Mitchell B Max

Publications and source records attributed to Mitchell B Max.

11 recordsLinked to original sources
PubMed1995

Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain.

The oxygen-15 water bolus positron emission tomography (PET) method was used to image regional brain activity in 4 patients with chronic post-traumatic neuropathic pain confined to one lower limb and in 1 patient with post-herpetic neuralgia. In comparison to 13 normal subjects, scans of the patients disclosed a statistically significant decrease in thalamic activity contralateral to the symptomatic side. Examination of the right/left ratio for all the subjects showed that the values for the patients fell at the extremes of the normal range, according to the side of the affected body part. These initial observations suggest that functional alterations in thalamic pain processing circuits may be an important component of chronic neuropathic pain.

Adult↗
PubMed1995

Effects of intravenous ketamine, alfentanil, or placebo on pain, pinprick hyperalgesia, and allodynia produced by intradermal capsaicin in human subjects.

The importance of N-methyl-D-aspartate (NMDA) receptor-mediated sensitization of central nervous system (CNS) neurons is well established in animal models of acute and chronic pain. A human model of central sensitization would be useful in screening new NMDA antagonists and establishing dose regimens for clinical trials in patients with pain related to sensitization of CNS neurons. We used this model to examine the effects of intravenous infusions of two centrally acting analgesics, the NMDA receptor antagonist ketamine and the morphine-like opioid agonist alfentanil. Twelve normal subjects completed a 3-session, randomized, double-blind, crossover study. From 25 to 60 min after capsaicin injection, subjects were given intravenous infusions of ketamine (mean dose: 32 mg), alfentanil (mean dose: 3075 micrograms), or saline placebo. Both drugs significantly reduced ongoing pain and pinprick-evoked hyperalgesia during the infusion. The reduction in allodynia evoked by light stroking was statistically significant only for alfentanil. Mean reduction +/- SEM relative to placebo were for ongoing pain: ketamine, 36 +/- 9%; alfentanil, 51 +/- 5%; area of pinprick hyperalgesia: ketamine, 34 +/- 7%; alfentanil, 35 +/- 7%; and area of mechanical allodynia: ketamine, 52 +/- 20%; alfentanil, 70 +/- 12%. Because the drugs were given systemically and produced side effects in all subjects, we cannot specify the site or sites of action nor conclusively rule out a non-specific 'active placebo' response as the cause for reduction of symptoms. Arguing against an 'active placebo' response, however, was the lack of analgesic effect of intravenous midazolam (mean dose; 3.4 mg, titrated to produce side effects of similar magnitude to ketamine and alfentanil) given at 145 min after capsaicin in 9 subjects who had received saline from 25 to 60 min. The results of this study suggest that neural systems sensitive to NMDA receptor antagonists and opioids participate in capsaicin-evoked pain phenomena, and support the feasibility of pharmacological studies using the intradermal capsaicin model.

Adult↗
PubMed1992

Transdermal clonidine versus placebo in painful diabetic neuropathy.

In a randomized, double-blind, 2-period crossover study, 24 patients with pain due to diabetic polyneuropathy received transdermal clonidine, 0.3 mg/day, and placebo patches, each for 6 weeks. Pain was assessed daily by a 13-word descriptor list. Mean daily pain scores for the 6th week, the primary outcome variable, averaged 13% lower with clonidine than with placebo (95% conf. lim. for clonidine effect: 29% reduction to 3% increase in pain), which was not statistically significant (P = 0.11, 2-tailed paired t test). After this study, however, 9 patients who wished to continue clonidine had single (3 patients) or multiple (6 patients) cycles of clonidine withdrawal and rechallenge. Seven of 9 patients consistently reported return of pain with patch withdrawal followed by relief upon retreatment. One patient had an equivocal response, and the other patient had no relief upon retreatment. The 7 responders appeared similar to the other 17 patients in pain quality and neurological exam. We conclude that there may be a subset of patients with diabetic polyneuropathy who respond to transdermal clonidine. Further research is needed to identify features of neuropathic pain that predict drug response and to develop study designs that are more sensitive to a response in a subset of patients.

Administration, Cutaneous↗
PubMed1991

Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial.

Although amitriptyline relieves pain in many patients with painful diabetic neuropathy, side effects often preclude effective treatment. Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants. We compared a 6 week course of desipramine (mean dose, 201 mg/day) to active placebo in 20 patients with painful diabetic neuropathy in a double-blind crossover trial. Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 with placebo. Pain relief tended to be greater in depressed patients, but relief was also observed in patients who did not show an antidepressant effect. We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy, offering an alternative for patients unable to tolerate amitriptyline. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressants proven effective in neuropathic pain, may mediate this analgesic effect.

Adult↗
PubMed1989

Single doses of the serotonin agonists buspirone and m-chlorophenylpiperazine do not relieve neuropathic pain.

A large body of evidence links serotonin with analgesia in animal models, but the lack of serotonin agonists suitable for clinical use has delayed study of serotonin's relevance to pain relief in humans. In a randomized, double-blind crossover study, we compared single doses of two 5-HT1 agonists, buspirone and m-chlorophenylpiperazine, to placebo in 20 patients with post-herpetic neuralgia or painful neuropathy. No analgesia was observed after either drug, at doses high enough to produce frequent central nervous system side effects. These results suggest that acute stimulation of 5-HT1 receptors is not sufficient to produce analgesia in patients with these neuropathic pain syndromes.

Adult↗
PubMed1985

The analgesic efficacy of intrathecal D-Ala2-D-Leu5-enkephalin in cancer patients with chronic pain.

D-Ala-D-Leu-enkephalin (DADL) is a pentapeptide which, compared to morphine, preferentially binds to the delta receptor. We compared the analgesic and side effects of intrathecal (i.t.) DADL and i.t. morphine sulfate (MS) in 10 tolerant cancer patients with chronic pain at or below the T12 level who were receiving inadequate relief or unacceptable side effects from systemic opiates. These patients were given i.t. DADL and i.t. MS in a randomized, double-blind, cross-over study on separate days at least 1 day apart. I.t. DADL produced analgesia in all patients tested. Total pain relief was greater with DADL than MS in 6 patients, equal in 1 patient and less with DADL in 3. Side effects, most commonly drowsiness, were similar with both MS and DADL and suggest supraspinal effects by both drugs. At the doses given i.t. DADL produced effective pain relief in patients tolerant to systemic opiates although no significant difference in analgesic efficacy between MS and DADL was observed. Studies of the relative analgesic potency of i.t. DADL in man are necessary to fully assess its value in those patients tolerant to systemic or i.t. opiates.

Adult↗