Neuro-endocrine function in older men with chronic pain : effects of chronic opioid usage.

Abstract

Background: There is increasing concern regarding adverse effects of long-term opioid medication use in non-cancer pain. Chronic opioid use has been shown to affect both the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. Hormonal deficiency due to chronic opioid use might contribute to altered pain sensitivity and functional decline. This may be more pronounced in the geriatric population who has poor functional reserve. Methods: A cross sectional study was performed looking at men over the age of 65 years, who have chronic non-malignant pain. Active arm subjects were taking continuous opioid treatment (≥ 4 weeks; dose equivalence ≥ 10mg oral morphine/day); control subjects were not receiving opioid treatment. Assessments included androgen studies (dehdroepiandrosterone sulphate (DHEA-S), testosterone, sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH), luteinizing hormone (LH)), waking salivary cortisol, low dose Synacthen test, neuropsychology testing, experimental cold pressor testing, cortisol testing during cold pressor testing, functional assessments (Instrumental Activities of Daily Living (IADL) Questionnaire, grip strength, and Timed Up and Go), Geriatric Depression Scale (GDS), Androgen Deficiency in Ageing Males Questionnaire (ADAM) and anthropometry. Results: Twenty-six subjects were enrolled and completed the study. There were 7 men in the active arm and 19 in the control arm. Opioid subjects had a reduced mean cortisol response 30, 60, 90 and 120 minutes post cold-pain testing compared with controls (p-value = 0.055, 0.003, 0.088, 0.046 respectively), suggesting impaired cortisol release following environmental stress. No statistical difference was seen in waking salivary cortisol or low dose Synacthen tests. There was no statistical difference between the two groups in measurements of the HPG axis. Opioid subjects performed significantly worse (mean 12 seconds) on Timed Up and Go compared to control subjects (mean 8.6 seconds; p-value = 0.036), however, the difference in grip strength and IADL scores between the two groups was not significant. Experimental pain threshold and tolerance and neuropsychology test results were not significantly different. Opioid subjects scored significantly higher on both ADAM (median opioid 8 vs. control 4; p-value = 0.0069) and GDS (median opioid 7 vs. control 1; p-value = 0.0024). Conclusion: These results suggest that older patients taking chronic opioid therapy for non-cancer pain have decreased cortisol response to stress. Given that little difference was seen in pain threshold and tolerance between the two groups, the blunted cortisol response is unlikely to be due to the effect of opioids reducing pain. This finding is important in the ageing population as it suggests that those on chronic opioid medication may not adapt well to additional stressors, which is one of the defining features of frailty. Results also suggest patients on chronic opioid therapy have poorer functional levels, and more symptoms of androgen deficiency and depression compared to chronic pain sufferers who are not taking opioid medication.