A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients

Abstract

Fibromyalgia is a diffuse chronic pain condition that occurs predominantly in women and may be under-reported in men. Symptoms include a loss of feeling of well-being and generalized widespread flu-like muscle aches and pain that fail to resolve due to central sensitization of nociceptive neurons. It has commonalities with a myriad of other chronic pain conditions which include PTSD, "Gulf War Syndrome", and various stress-induced conditions caused, for example, by viral infection, emotional or physical stress, trauma, combat, accident or surgery. It is not understood why some individuals are susceptible to this condition and others are not. White et al., elsewhere in this issue, present a clinical feasibility study designed to test the hypothesis that 1) low or deficient testosterone serum levels are linked to a high risk for an inflamed nociceptive nervous system and resultant chronic pain states, and 2) a testosterone transdermal gel applied once a day by fibromyalgia patients can be an effective therapeutic against chronic pain. Here, a short profile of fibromyalgia is provided along with a brief summary of best practices currently recommended by clinical specialists. The link between testosterone and pain is then discussed, with an overview of scientific studies that lay the foundation for testosterone as a possible important additional therapeutic that has the potential to be safely administered and effective but also avoid the adverse effects of other therapeutics. Finally, novel mechanisms by which testosterone therapy is likely to down-modulate pain signaling are proposed.

Cortisol, testosterone, and pain levels among patients undergoing McKenzie therapy and suboccipital relaxation

“…A suppressing effect of testosterone on the hypothalamic-pituitary-adrenal (HPA) axis has been observed [24]. Furthermore, it has been proven to affect pain perception in patients with fibromyalgia and other diseases [38]. There is a correlation between gonadectomy and increased susceptibility to pain in rats [39,40].…”

Neural responses in the pain matrix when observing pain of others are unaffected by testosterone administration in women

“…Relating to our current findings, it might thus be that T does not affect aversive responding. Although with regards to personal distress, some research has noted that T is associated with reduced pain perception in men and women (Choi, Chung and Lee 2012;Bartley et al 2015;White and Robinson 2015). This interpretation highlights the importance of publishing null findings, especially in the light of the current criticism on the possible publication bias in oxytocin administration studies (Lane et al 2016).…”

“…Hormonal factors can also affect empathy for pain, as the neuropeptide oxytocin has shown to decrease neural activation of the pain circuitry upon seeing pain in others, an effect that was independent of group status of the observed other . In addition, studies showing an association between experienced self-pain and endogenous or exogenous T in men and women (Choi, Chung and Lee 2012;Bartley et al 2015;White and Robinson 2015) suggest that empathy towards pain in others is also affected by T. But if T alters neural responses to pain in others, and whether this would depend on ethnicity of the outgroup are currently unknown. Therefore, in the current study, we investigate the effect of T on neural empathic responses to pain in others.…”

Hormones in pain modulation and their clinical implications for pain control: a critical review

“…49 In terms of clinical implications, sex hormones may help in the treatment of chronic pain and testosterone has been found to be effective in treating central sensitization in fibromyalgia patients. 50 Additional research is warranted to further elucidate the mechanisms of sex differences in pain to facilitate sex-specific treatments that consider both biological and psychological factors.…”