Purpose: This study aimed to investigate the hypothalamic-pituitary-adrenal (HPA) axis in spinal cord injury (SCI)-related neuropathic pain (NP) using dynamic adrenocorticotropic hormone (ACTH) stimulation tests.
Methods: This case-control study was conducted with 22 patients diagnosed with traumatic chronic spinal cord injury (15 with and 7 without neuropathic pain) and ten age- and sex-matched healthy control subjects. Collected data included socio-demographic variables, SCI characteristics, and level of NP using a numeric rating scale (NRS) and the Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS). HPA axis function was measured via low-dose (1 μg) and standard-dose (250 μg) ACTH tests (LDT and SDT, respectively).
Results: No significant differences existed regarding peak cortisol responses or area under the curve (AUC) of cortisol responses between the SCI patients with NP and healthy controls using LDT and SDT. In the SCI patients without pain, cortisol responses were significantly lower than those in the healthy controls for LDT and SDT. Peak cortisol and AUC responses of the LDT and SDT were positively correlated with NRS in SCI patients with NP.
Conclusions: This study demonstrated that, in chronic SCI patients with NP, basal cortisol levels are relatively higher compared to healthy controls, and that HPA axis can be activated with low- and standard-dose ACTH stimulation tests. Although NP following SCI was not significantly associated with hypo- or hypercortisolemia, either after low- or standard-dose ACTH stimulation test, the severity of NP during chronic SCI may be positively associated with HPA axis activity.
Keywords: ACTH; Glucocorticoids; Hypothalamus; Neuralgia; Pain; Pituitary–adrenal system; Spinal cord injuries.