The journal of pain : official journal of the American Pain Society
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To evaluate the role of sigma receptors in the sexually dimorphic antianalgesic effect of agonist-antagonist kappa opioids, 2 neuroleptics, haloperidol, a sigma receptor antagonist, and chlorpromazine, which has minimal effect at sigma receptors, were administered with the agonist-antagonist kappa opioid nalbuphine in patients with postoperative pain. Before surgical extraction of bony impacted mandibular third molar teeth, patients received haloperidol (1 mg), chlorpromazine (10 mg), or placebo by oral administration. After surgery, the pain intensity did not differ significantly between the 3 treatment groups, suggesting lack of analgesic effect produced by either haloperidol or chlorpromazine. All patients were then administered nalbuphine (5 mg, intravenous). As previously reported, the group that did not receive a preoperative neuroleptic exhibited sexually dimorphic analgesia, with women experiencing greater analgesia than men. Antianalgesia was also observed, with men experiencing late onset increased pain compared with baseline, starting approximately 1 hour after nalbuphine administration. Both neuroleptics blocked nalbuphine antianalgesia, resulting in enhanced analgesia and elimination of the sex differences. Because chlorpromazine and haloperidol enhanced nalbuphine analgesia and eliminated sexual dimorphism, the receptor at which neuroleptics act to antagonize the "antianalgesia" might be a common site of action to both drugs. ⋯ This study demonstrates that neuroleptics can block the antianalgesic effect of agonist-antagonist kappa opioids. These findings could help inform the development of novel analgesics.
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Comparative Study
Pain assessment in patients with low back pain: comparison of weekly recall and momentary electronic data.
Electronic data collection for monitoring pain has become increasingly popular in clinical research. Past research has shown that electronic diaries improve the timeliness of receipt of data, contribute to higher rates of compliance, and are preferred by patients over paper diaries, and this research suggests that electronic diaries that capture current pain at the moment of reporting result in more reliable ratings than recalled pain ratings. This study compared differences of momentary pain intensity ratings on an electronic visual analog scale (VAS) with weekly recalled pain on a 0 to 10 scale. We asked 21 patients with chronic low back pain to monitor their current pain at least once a day by using a VAS for up to 1 year with a palmtop computer. They were also called once a week and asked to rate their recalled weekly pain orally on a numeric scale from 0 to 10. Patients entered data electronically on average 357 times, for an average of 7.8 times a week. We found that (1) weekly recalled pain agreed highly (r > .90) with averaged momentary pain assessments, (2) neither frequency of electronic monitoring nor variability in momentary pain ratings (high standard deviations) contributed to degree of agreement between momentary and recalled pain, and (3) a ceiling effect was observed in VAS pain ratings as compared with numeric pain ratings. These findings suggest that, among many individuals, weekly recalled pain might be just as useful as momentary data collected through electronic data entry. ⋯ Some believe that remembered pain is problematic because of recall bias and that data from frequent momentary pain ratings with electronic diaries are more valid. This study demonstrates that recalled pain is as valid as momentary data for many patients.
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In most published studies women are more sensitive to experimental pain than men. Enhanced central pain processing in women has been suggested, but psychosocial factors might also have affected the findings. Data from five completed healthy volunteer studies were analyzed to investigate gender differences in development of secondary hyperalgesia. Cutaneous hyperalgesia was induced with the heat/capsaicin sensitization model. Outcome measures were areas of secondary hyperalgesia to brush and von Frey hair stimulation after heat and capsaicin sensitization, rating of pain during heat/capsaicin sensitization, and heat pain detection thresholds. There was a trend toward smaller areas of secondary hyperalgesia in women. After adjusting for estimated gender differences in forearm surface area, areas to brush but not von Frey hair stimulation after capsaicin sensitization were larger in women. Peak pain, but not total pain, during prolonged noxious thermal stimulation was higher in women. There was no gender difference in pain ratings during capsaicin sensitization or in heat pain detection thresholds. The results provided only limited support to the hypothesis that gender differences in clinical pain syndromes can be explained by enhanced central sensitization in women. ⋯ Our findings suggest that gender differences in nociceptive transmission and neuronal sensitization are small and provide only limited support to the hypothesis that gender differences in acute and chronic pain syndromes can be explained by enhanced central sensitization in women.
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Clinical Trial
Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency.
We conducted a 24-week open-label pilot study of testosterone (T) patch therapy in 23 men with opioid-induced androgen deficiency (OPIAD). The T dosage was 5 mg/day for the first 12 weeks and 7.5 mg/day for the second 12 weeks. Seven subjects discontinued prematurely: 4 for noncompliance, 2 for skin irritation and 1 for hepatitis C treatment. In the "completers" population (n = 16), mean (SD) free T levels (normal range 52 to 280 pg/mL) were 28.5 (18.6) pg/mL at baseline, 72.8 (29.6) pg/mL on 5 mg/day (P < .001 vs. baseline), and 120.2 (69.5) pg/mL on 7.5 mg/day (P < .001 vs. baseline and P < .01 vs. 5 mg/day). Total T, dihydrotestosterone, and estradiol showed parallel changes. Sex hormone-binding globulin levels were elevated at baseline and decreased modestly with treatment (P < .05 vs. baseline at 5 mg/day; P < .01 vs. baseline at 7.5 mg/day). Luteinizing hormone levels were in the low-normal range at baseline and suppressed markedly with treatment (P < .001 vs. baseline at both doses). Androgen deficiency symptoms (ADSQ), sexual function (Watts SFQ), mood (PGWB), depression (BDI-II), and hematocrit levels showed improvement during treatment, generally more so at the 7.5 mg/day dosage (P < .001 vs. baseline for most parameters). Pain scores (BPI-SF) decreased slightly on 7.5 mg/day (interference score: P < .05 vs. baseline and 5 mg/day); the use of opioids did not change appreciably. The testosterone patches were generally well tolerated. ⋯ Long-acting opioid preparations suppress the hypothalamic-pituitary-gonadal axis in men and produce a symptomatic state of opioid-induced androgen deficiency (OPIAD). Testosterone patch therapy at a dose of 7.5 mg/day normalizes hormone levels and appears to improve a number of quality of life parameters (eg, sexual function, well-being, mood) in men with OPIAD.
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The current study compared the psychometric properties of 2 commonly used measures of pain-related interference, the Graded Chronic Pain (GCP) Disability scale and 3 modified versions of the Brief Pain Inventory (BPI) Interference scale. Participants were 127 persons with spinal cord injury (SCI) who reported pain on a survey. The results suggest that the GCP Disability scale and 3 versions of the BPI Interference scale are reliable and valid measures of pain-related interference in persons with SCI and pain. All 4 measures evidenced excellent internal consistency. The composite scores and individual items of the GCP Disability scale and each version of the BPI Interference scale were significantly related to average pain intensity during the past week and a global measure of psychological functioning. Finally, as pain intensity ratings increased (from mild to moderate to severe), so did the composite and item-level ratings of interference for each version of the BPI Interference scale and GCP Disability scale. Strengths and weaknesses of each measure for use with persons with disability and pain are discussed. ⋯ The GCP Disability scale and 3 versions of the BPI Interference scale (modified for use in persons with disabilities) appear to be reliable and valid measures of pain-related interference in persons with SCI. Future research should examine their psychometric properties in other disability populations.