Neuroendocrine evaluation of central opiate activity in primary headache disorders

Abstract

The evaluation of central opiate activity could be of clinical value in the diagnosis and treatment of pain syndromes. The current approach via direct measurement of endogenous opioid peptides in cerebrospinal fluid (CSF) is not devoid of side effects and cannot be used in every-day practice. As an alternative to this method, we have studied the neuroendocrine response of plasma LH to an i.v. naloxone injection in 39 headache sufferers from different diagnostic subgroups, and in 12 age- and sex-matched healthy volunteers. Patients (19 females and 20 males) were affected by common migraine (CM, 11 cases), migraine with interparoxysmal headache (MIH, 9), classical migraine (C1M, 9), and chronic cluster headache (CH, 10). Headache lasted 3–36 years. Prior to naloxone challenge (4 mg i.V.), LH pulsatility was evaluated for 1 h. The next morning, the pituitary response to LH-RH (10 μg i.v.) was tested in 20 patients. Plasma LH was measured by RIA in every sample. The response to the tests was evaluated as secretion area of plasma LH minus the mean basal value. Controls (497.5 ± 85.5 mIU/ ml × 120 min), CIM (357.8 ± 78.9) and CH (450.5 ± 70.4) patients showed similar results, while in cases of CM (155.3 ± 71.7, P < 0.05) and MIH (104.1 ± 53.7, P < 0.01) the LH secretion after naloxone injection was significantly blunted. On the contrary, the response of LH to LH-RH was similar in controls and patient groups, thus excluding pituitary dysfunctions in this response. Given the fact that there are some limitations related to the modulatory effects of gonadal steroids, these data suggest the use of the naloxone test as a tool for exploring the central opiate activity in primary headache disorders, mainly in migraine syndromes. Indeed, the naloxone test fails in those diagnostic subgroups characterized by impaired CSF levels of endogenous opioids.