Blunted ACTH and Cortisol Responses to Systemic Injection of Corticotropin‐Releasing Hormone (CRH) in Fibromyalgia

Abstract

Thirteen female patients suffering from fibromyalgia (FM) and thirteen female age-matched controls were intravenously injected with a bolus dose of 100 microg corticotropin-releasing hormone (CRH), and the evoked secretion pattern of ACTH, cortisol, somatostatin, and growth hormone (GH) was followed up for two hours, together with the plasma levels of CRH. The increases of ACTH and cortisol following CRH were not significantly different between controls and FM patients. The increase of plasma CRH following its injection was significantly higher in FM patients and lasted about 45 min, paralleled by an increase of somatostatin with a similar time course. Basal GH levels were significantly lower in FM patients. GH increased in FM patients 90 min after injection of CRH, coincident with decreasing CRH and somatostatin levels, while GH levels in controls rather decreased with the lowest values occurring 90 min after CRH. The results support the concept that the hormonal secretion pattern frequently observed in FM patients is primarily caused by CRH, possibly as a response to chronic pain and stress. The elevated levels of CRH in the circulation of FM patients suggest elevated levels of CRH-binding protein, which could explain why the levels of ACTH and cortisol between controls and FM following CRH do not differ.

Funktionsst�rung der hypothalamisch-hyphophys�r-adrenalen Achse bei Patienten mit akuten, chronischen und intervallartigen Schmerzsyndromen

“…B. bei akuten Myokardischämien [30,35] und postoperativen Schmerzen, wobei als Ursache sowohl der Schmerz selbst als auch eine sekundäre neuroendokrine Stressantwort diskutiert werden []. Bei chronischen oder intervallartigen Schmerz-oder Stresssituationen wie der Fibromyalgie oder dem Clusterkopfschmerz entfaltet die hypothalamischhypophysär-adrenale Achse eine teleologisch schwer zu deutende Wirkung, wobei sowohl ein Hyper- [33] als auch ein Hypokortisolismus [7] als Folge einer vielfach dokumentierten Dysregulation [27] beschrieben sind. Die Interpretation der Daten wird insbesondere durch die häu-fige Koinzidenz chronischer Schmerzen mit einer begleitenden Depression [ …”

Cerebrospinal Fluid Corticotropin-Releasing Factor Concentration is Associated with Pain but not Fatigue Symptoms in Patients with Fibromyalgia

“…Early life stress has also been associated with alterations in adult CSF CRF levels, in both preclinical and clinical studies (Carpenter et al, 2004;Heim et al, 2004), and recent study results indicate that that early life stress influences stress system function in adults with FM (McLean et al, 2005b;Weissbecker et al, 2005). In the single study assessing CRF levels in FM patients to date, Riedel et al (2002) found higher baseline serum CRF levels in FM patients vs healthy controls. To date, we are not aware of any studies that have examined CSF CRF concentrations among patients with FM.…”

Aspects of Pain, Its Assessment and Evaluation from An Acupuncture Perspective

“…Woolf recently proposed a categorisation of pain based on its mechanisms, into: nociceptive -transient pain in response to a noxious stimulus; inflammatory -spontaneous pain and hypersensitivity to pain in response to tissue damage and inflammation; neuropathic -spontaneous pain and hypersensitivity to pain in association with damage to or a lesion of the nervous system; functional -hypersensitivity to pain resulting from abnormal central processing of normal input. 27 Biochemical markers of pain associated symptoms In long term pain conditions, associated symptoms of physiological and psychological distress are reported, 22 as well as anxiety and depression. 23;24 From a physiological perspective, an aberrant function of the sympathetic nervous system, 28 the hypothalamicpituitary-adrenal (HPA) axis, 29 or its negative feedback loop, 30;31 have been discussed as plausible causes of the stress related symptoms in pain conditions like fibromyalgia.…”

“…20;21 Along term pain condition is also reported as associated with affective components like depression and anxiety. [22][23][24] Pain mechanism Depending on the aetiology, pain has been classified into different categories, 25;26 each with its own characteristics. Woolf recently proposed a categorisation of pain based on its mechanisms, into: nociceptive -transient pain in response to a noxious stimulus; inflammatory -spontaneous pain and hypersensitivity to pain in response to tissue damage and inflammation; neuropathic -spontaneous pain and hypersensitivity to pain in association with damage to or a lesion of the nervous system; functional -hypersensitivity to pain resulting from abnormal central processing of normal input.…”

“…Corticotropin releasing factor, CRF, synthesised in the hypothalamic paraventricular nuclei, is reported as one physiological mediator of different endocrine, autonomic, and behavioural responses to stress. [32][33][34] Elevated plasma and cerebrospinal fluid (CSF) concentrations of CRF have been found in patients with fibromyalgia, 22 and in patients with posttraumatic stress disorder. 35 Hyperactive CRF neurons have, therefore, been suggested to play a role in the nociceptive and psychological mechanisms in fibromyalgia.…”