Patients treated with long-term spinal infusion of high doses of morphine develop a granuloma at the location of the catheter tip. Diagnosis is based on a steady increase in intrathecal morphine dosage after a relatively prolonged period of stability, on the gradual development of neurologic signs and symptoms suggesting radicular or spinal cord compression, and on magnetic resonance images. We describe a man with central neuropathic pain after removal of a tumor. The presence of all 3 of the aforementioned diagnostic criteria led to suspicion of a spinal granuloma.

The nucleus accumbens is considered a critical target of the action of drugs of abuse. In this nucleus a "shell" and a "core" have been distinguished on the basis of anatomical and histochemical criteria. The present study investigated the effect in freely moving rats of intravenous cocaine, amphetamine, and morphine on extracellular dopamine concentrations in the nucleus accumbens shell and core by means of microdialysis with vertically implanted concentric probes. Doses selected were in the range of those known to sustain drug self-administration in rats. Morphine, at 0.2 and 0.4 mg/kg, and cocaine, at 0.5 mg/kg, increased extracellular dopamine selectivity in the shell. Higher doses of cocaine (1.0 mg/kg) and the lowest dose of amphetamine tested (0.125 mg/kg) increased extracellular dopamine both in the shell and in the core, but the effect was significantly more pronounced in the shell compared with the core. Only the highest dose of amphetamine (0.250 mg/kg) increased extracellular dopamine in the shell and in the core to a similar extent. The present results provide in vivo neurochemical evidence for a functional compartmentation within the nucleus accumbens and for a preferential effect of psychostimulants and morphine in the shell of the nucleus accumbens at doses known to sustain intravenous drug self-administration.

Buprenorphine was evaluated for its abuse potential and utility in treating narcotic addiction. The drug was morphine-like but was 25 to 50 times more potent than morphine and was longer-acting. Little if any physical dependence of clinical significance was produced by buprenorphine. The effects of morphine to 120-mg doses were blocked by buprenorphine, a blockade that persisted for 29 1/2 hours. In man, buprenorphine has less intrinsic activity than morphine, and as such, as a low abuse potential. Moreover, the drug has potential for treating narcotic addiction since it is acceptable to addicts, is long-acting, produces a low level of physical dependence such that patients may be easily detoxified, is less toxic than drugs used for maintenance therapy, and blocks the effects of narcotics.

BACKGROUND. Extreme hormonal and metabolic responses to stress are associated with increased morbidity and mortality in sick adults. We hypothesized that administering deep opioid anesthesia to critically ill neonates undergoing cardiac surgery would blunt their responses to stress and might improve clinical outcomes. METHODS. In a randomized trial, 30 neonates were assigned to receive deep intraoperative anesthesia with high doses of sufentanil and postoperative infusions of opiates for 24 hours; 15 neonates were assigned to receive lighter anesthesia with halothane and morphine followed postoperatively by intermittent morphine and diazepam. Hormonal and metabolic responses to surgery were evaluated by assay of arterial blood samples obtained before, during, and after the operations. RESULTS. The neonates who received deep anesthesia (with sufentanil) had significantly reduced responses of beta-endorphin, norepinephrine, epinephrine, glucagon, aldosterone, cortisol, and other steroid hormones; their insulin responses and ratios of insulin to glucagon were greater during the operation. The neonates who received lighter anesthesia (with halothane plus morphine) had more severe hyperglycemia and lactic acidemia during surgery and higher lactate and acetoacetate concentrations postoperatively (P less than 0.025). The group that received deep anesthesia had a decreased incidence of sepsis (P = 0.03), metabolic acidosis (P less than 0.01), and disseminated intravascular coagulation (P = 0.03) and fewer postoperative deaths (none of 30 given sufentanil vs. 4 of 15 given halothane plus morphine,(P less than 0.01). CONCLUSIONS. In neonates undergoing cardiac surgery, the physiologic responses to stress are attenuated by deep anesthesia and postoperative analgesia with high doses of opioids. Deep anesthesia continued postoperatively may reduce the vulnerability of these neonates to complications and may reduce mortality.

The respiratory effects of two postoperative analgesic regimens were compared in two groups of 16 patients each, recovering from general anesthesia and major surgery. One group received a pain-relieving dose of iv morphine (mean, 18.1 mg), with the same dose repeated as a continuous intravenous infusion over the subsequent 24 h. The other group received regional anesthesia using bupivacaine. The patients were monitored for 16 h after surgery. The two analgesic regimens provided patients with comparable analgesia throughout the study period, but there were quite different respiratory effects in the two groups. Ten patients receiving morphine infusions had a total of 456 episodes of pronounced oxygen desaturation (SaO2 less than 80%). These occurred only while the patients were asleep, and all were associated with disturbances in ventilatory pattern, namely, obstructive apnea (144 episodes in eight patients), paradoxic breathing (275 episodes in six patients), and period of slow ventilatory rate (37 episodes in one patient). In contrast, in patients receiving regional anesthesia, oxygen saturation never decreased below 87%. Central apnea, obstructive apnea, and paradoxic breathing occurred more frequently in patients in the morphine group (12, 10, and 10 patients, respectively) than patients in the regional anesthesia group (4, 3, and 5 patients, respectively). The interaction of sleep and morphine analgesia produced disturbances in ventilatory pattern, causing profound oxygen destruction. These results suggest that postoperative pain relief using regional anaesthesia has a greater margin of safety in terms of respiratory side effects than does the continuous administration of opiates.

BACKGROUND: The use of opioid analgesics for chronic non-cancer pain is controversial. Some surveys report good pain relief and improvement in performance while others suggest a poor outcome with a propensity to psychological dependence or addiction. METHODS: We undertook a randomised double-blind crossover study to test the hypothesis that oral morphine relieves pain and improves the quality of life in patients with chronic regional pain of soft tissue or musculoskeletal origin who have not responded to codeine, anti-inflammatory agents, and antidepressants. Morphine was administered as a sustained-release preparation in doses up to 60 mg twice daily and compared with benztropine (active placebo) in doses up to 1 mg twice daily over three-week titration, six-week evaluation, and two-week washout phases. Pain intensity, pain relief, and drug liking were rated weekly and psychological features, functional status, and cognition were assessed at baseline and at the end of each evaluation phase. FINDINGS: After dose titration in the 46 patients who completed the study, the mean daily doses of drugs were morphine 83.5 mg and benztropine 1.7 mg. On visual analogue scales, the morphine group showed a reduction in pain intensity relative to placebo in period I (p = 0.01) and this group also fared better in a crossover analysis of the sum of pain intensity differences from baseline (p = 0.02). No other significant differences were detected. INTERPRETATION: In patients with treatment-resistant chronic regional pain of soft-tissue or musculoskeletal origin, nine weeks of oral morphine in doses up to 120 mg daily may confer analgesic benefit with a low risk of addiction but is unlikely to yield psychological or functional improvement.

BACKGROUND. Opioids can produce potent antinociceptive effects by interacting with local opioid receptors in inflamed peripheral tissue. In this study we examined the analgesic effects of the intraarticular, as compared with intravenous, administration of morphine after arthroscopic knee surgery. METHODS. In a double-blind, randomized trial, we studied 52 patients who had received one of four injections at the end of surgery. The patients in group 1 (n = 18) received 1 mg of morphine intraarticularly and saline intravenously; those in group 2 (n = 15), saline intraarticularly and 1 mg of morphine intravenously; those in group 3 (n = 10), 0.5 mg of morphine intraarticularly and saline intravenously; and those in group 4 (n = 9), 1 mg of morphine and 0.1 mg of naloxone intraarticularly and saline intravenously. The volume of the intraarticular injections was 40 ml, and that of the intravenous injections was 1 ml. After 1, 2, 3, 4, 6, and 24 hours, postoperative pain was assessed with a visual-analogue scale, a numerical-rating scale, and the McGill pain questionnaire. The need for supplemental analgesic agents, the patients' vital signs, and the occurrence of side effects were monitored. RESULTS. All pain scores were lower in group 1 than in group 2 at all times. The differences were significant (P less than 0.05) at three, four, and six hours (mean [+/- SD] visual-analogue score at six hours, 9 +/- 13 mm vs. 37 +/- 31 mm). The mean (+/- SD) consumption of supplemental analgesic medication per 24 hours was significantly lower in group 1 (36 +/- 51 mg of diclofenac and 1.2 +/- 3.4 mg of meperidine) than in group 2 (75 +/- 42 mg of diclofenac and 14 +/- 18 mg of meperidine, P less than 0.05). The visual-analogue scores in group 3 were slightly but not significantly higher than those in group 1 at all times except 6 and 24 hours after injection. The visual-analogue scores were significantly higher in group 4 than in group 1 one to four hours after injection (P less than 0.05), indicating that the analgesic effect of intraarticular morphine was reversible by naloxone. CONCLUSIONS. Low doses of intraarticular morphine can significantly reduce pain after knee surgery through an action specific to local opioid receptors that reaches its maximal effect three to six hours after injection.