Gender-related effects of chronic non-malignant pain and opioid therapy on plasma levels of macrophage migration inhibitory factor (MIF)

Abstract

Macrophage migration inhibitory factor (MIF) is a cytokine produced by neuroendocrine and immune tissues that possesses several characteristics of a neuroendocrine mediator. Chronic pain is known to affect and to be affected by neuroendocrine and immune mechanisms. In the present study, the plasma levels of MIF and several hormones (cortisol, estradiol, testosterone) were determined to evaluate their mutual behaviour in controls and in chronic pain patients. Blood samples were collected from males and females divided into groups depending on their age (younger or older than 55) and health condition: (1) pain-free control subjects; (2) chronic non-malignant pain subjects. Moreover, two additional groups were added to evaluate the effects of short- and long-term opioid administration: (3) short-term opioid-treated chronic pain patients and (4) long-term opioid-treated chronic pain patients (longer than 6 months). MIF in control/younger men was higher than in all the other control and chronic pain groups. MIF was lower in pain patients than in controls of both sexes. MIF was not changed by morphine administration; its levels remained lower in opioid-treated subjects than in controls after both short- and long-lasting administration. Chronic pain changed hormone plasma levels differently in male and female patients. MIF was positively correlated with testosterone and negatively with estradiol. These results demonstrate sex differences in the younger men and women and a strong pain-induced decrease of MIF availability. These findings suggest the involvement of this cytokine in the sex differences observed in chronic pain conditions.

Endocrine and behavioural effects of transdermal buprenorphine in pain-suffering women of different reproductive ages

“…In contrast to findings obtained with other opioids [6], in which testosterone was drastically decreased, neither TT nor fT changed significantly due to Buprenorphine TDS treatment in either group of women throughout the 6-month period (Table 3); in fact, there was a slight tendency to an increase in both groups. The TT and fT levels were slightly higher in the post-M women at all determinations.…”

“…Therefore, it is mandatory to choose a treatment able to avoid this effect. mainly occurs in men treated with opioids, but it has also been found in women [6,12]. Its symptoms are fatigue, anaemia, changes in skin features, absence of libido, bad mood and depression.…”

“…lasting hypogonadism [6], a clinical syndrome associated with many physical and cognitive complaints [7]. Indeed there is substantial evidence that gonadal hormones can influence the structure and functions of neurones not only during puberty but also in adulthood, including alterations of their dendrites and synaptic connections.…”

“…It has also been suggested that androgens might be an effective therapy for certain neurological dysfunctions such as Alzheimer's disease and schizophrenia [8][9] and that they can modulate pain [10][11]. The effects on androgens have mostly been described in men, although opioid-induced hypogonadism with clinically relevant features has also been shown in women [6,12].…”

Studying sex and gender differences in pain and analgesia: A consensus report

“…Repeated episodes of formalin testing engender adaptations in nociception that are gonadal hormone-dependent [7,31], suggesting that pain chronicity is indeed an important factor to consider in future preclinical studies of sex differences in pain/ analgesia. The extent to which chronic pain or analgesic use alters an individual's circulating gonadal hormones (e.g., [8,10,47,104]), which can in turn affect their pain/analgesic sensitivity, should also be considered.…”