Opioids for Chronic Nonterminal Pain

Jane C. Ballantyne, MD, FRCA


South Med J. 2006;99(11):1245-1255. 

In This Article

Hormonal and Immune Effects

Long-term opioid use results in clinically relevant suppression of both hypothalamopituitary-adrenal and -gonadal axes, with suppression in luteinizing hormone, follicle-stimulating hormone, testosterone, estrogen and cortisol.[50,51,52] These effects have been demonstrated in addicts, past addicts treated with methadone maintenance[50] and more recently, in opioid-treated chronic pain patients.51 The effects are most prominent in patients treated with intrathecal opioids.[53,54,55] The gonadal effects can result in male and female infertility and in decreased libido, drive and aggression. Clinically, testosterone deficiency is the most frequently manifest of the deficiencies, and male patients can benefit from testosterone replacement.[54,56] Although the suppressive effect of opioids on the endocrine system seems clear, determining the exact contribution to health of these effects is not straightforward. Most chronic pain patients present with complex medical and psychosocial histories, and many have underlying neuroendocrine derangements, either because of coexisting medical illness, or because of the effects of their treatment. Thus, even knowing the likely direct effects of opioids on endocrine function, their exact clinical relevance in an individual patient is not clear.

Opioid drugs may affect immunity through their neuroendocrine effects, or through direct effects on the immune system. Preclinical research has shown that opioids alter the development, differentiation and function of immune cells, and opioid receptors have been demonstrated on immune cells.[57,58] Evidence of immune modulation in humans is limited, but opioids have been shown to exacerbate immunosuppression in HIV patients, which suggests that prolonged opioid use may affect the immune system, at least in immunocompromised persons.[59] There are no studies of immune function in patients receiving long-term opioid therapy for chronic pain, but the direct evidence that opioids impair immune function in susceptible individuals is concerning. Pain itself can suppress immune function, so patients receiving prolonged opioid therapy without good pain relief are probably the most vulnerable.


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