Intrathecal administration of opioids is a very efficient tool in the long-term control of intractable nonmalignant pain. However, despite the well known role of opioids in endocrine regulation, few data are available about possible effects on hypothalamic-pituitary function during this treatment.Seventy-three patients (29 men and 44 women; mean age, 49.2 Ϯ 11.7 yr) receiving opioids intrathecally for nonmalignant pain were enrolled for extensive endocrine investigation. At the time of hormonal determination, the mean duration of opioid treatment was 26.6 Ϯ 16.3 months; the mean daily dose of morphine was 4.8 Ϯ 3.2 mg. The control group consisted of 20 patients (11 men and 9 women; mean age, 54.2 Ϯ 14.0 yr) with a comparable pain syndrome but not treated with opioids.Decreased libido or impotency was present in 23 of 24 men receiving opioids. The serum testosterone level was below 9 nmol/L in 25 of 29 men and was significantly lower than that in the control group (P Ͻ 0.001). The free androgen index was below normal in 18 of 29 men and was significantly lower than that in the control group (P Ͻ 0.001). The serum LH level was less than 2 U/L in 20 of 29 men and was significantly lower than that in the control group (P Ͻ 0.001). Serum FSH was comparable in both groups. Decreased libido was present in 22 of 32 women receiving opioids. All 21 premenopausal females developed either amenorrhea or an irregular menstrual cycle, with ovulation in only 1. Serum LH, estradiol, and progesterone levels were lower in the opioid group. In all 18 postmenopausal females significantly decreased serum LH (P Ͻ 0.001) and FSH (P ϭ 0.012) levels were found. The 24-h urinary free cortisol excretion was below 20 g/day in 14 of 71 opioid patients and was significantly lower than that in the control group (P ϭ 0.003). The peak cortisol response to insulin-induced hypoglycemia was below 180 g/L in 9 of 61 opioid patients and was significantly lower than that in the nonopioid group (P ϭ 0.002). The insulin-like growth factor I SD score was below Ϫ2 SD in 12 of 73 opioid patients and was significantly lower than that in the control group (P ϭ 0.002). The peak GH response to hypoglycemia was below 3 g/L in 9 of 62 subjects and was significantly lower than that in the control group (P ϭ 0.010). Thyroid function tests and PRL levels were considered normal. No metabolic disturbances were recorded, apart from significantly decreased high density lipoprotein cholesterol levels (P ϭ 0.041) and elevated total/high density lipoprotein cholesterol ratio (P ϭ 0.008) in the opioid group compared to the control group. Supplementation with gonadal steroids improved sexual function in most patients.In conclusion, of all patients receiving intrathecal opioids, the large majority of men and all women developed hypogonadotropic hypogonadism, about 15% developed central hypocorticism, and about 15% developed GH deficiency. These findings suggest that further investigations are required to determine the need for systematic endocrine work-up in these pa...

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We have studied the effect of adding ketamine to i.v. morphine patient-controlled analgesia (PCA) for the treatment of pain after laparotomy. Thirty patients were allocated randomly to receive PCA with saline or ketamine in a double-blind, randomized study. Analgesia was started in the recovery room when visual analogue scale (VAS) scores were > 4. A bolus dose of morphine 3 mg was given to all the patients followed by i.v. PCA. Simultaneously, an infusion of ketamine 2.5 micrograms kg-1 min-1 or saline was started. Pain scores, morphine consumption and side effects were noted for up to 48 h after the start of PCA. VAS scores decreased significantly with time (P = 0.0001) and were similar (P = 0.3083) in both groups. Cumulative morphine consumption at 48 h was significantly lower in the ketamine group (28 mg) than in the control group (54 mg) (P = 0.0003). Nausea was less frequent in the ketamine group (P = 0.03).

In a double-blind, placebo controlled crossover study, the effect of morphine on the affective and sensory pain ratings in different forms of chronic pain was investigated. Six patients suffering from central neurogenic pain, 8 from peripheral neurogenic pain and 6 from idiopathic pain participated in the study. Morphine (0.3 mg/kg bodyweight) and placebo (saline) were administered intravenously. Both the affective and sensory dimensions of pain sensation were assessed by means of the 101-point rating scale. From our results it appeared that morphine reduced the affective but not the sensory dimension of pain sensation in both groups of neurogenic pain patients. In the idiopathic pain group, neither the affective nor the sensory dimension of pain sensation were affected. The observed differences in opioid responsiveness were neither the result of differences in opioid consumption nor of differences in baseline pain levels.

The Dutch version of the McGill Pain Questionnaire was composed mainly by following R. Melzack's methodological design. The recommendations of the Finnish research team were considered and integrated. In the first phase as wide an inventory of pain descriptions as possible was drawn up. In the second phase, these pain descriptions were categorized by pain experts and students according to quality aspects. In the third phase the pain descriptions were judged according to intensity aspect as well by pain experts, by students and by pain patients. Finally a fourth phase was set up to obtain insight into the reliability and validity of the McGill Pain Questionnaire - Dutch Version (MPQ-DV).