Recombinant human growth hormone improves cognitive capacity in a pain patient exposed to chronic opioids

Abstract

During recent decades, the increasing use of opioids for chronic non-cancer pain has raised concerns regarding tolerance, addiction, and importantly cognitive dysfunction. Current research suggests that the somatotrophic axis could play an important role in cognitive function. Administration of growth hormone (GH) to GH-deficient humans and experimental animals has been shown to result in significant improvements in cognitive capacity. In this report, a patient with cognitive disabilities resulting from chronic treatment with opioids for neuropathic pain received recombinant human growth hormone (rhGH) replacement therapy. A 61-year-old man presented with severe cognitive dysfunction after long-term methadone treatment for intercostal neuralgia and was diagnosed with GH insufficiency by GH releasing hormone-arginine testing. The effect of rhGH replacement therapy on his cognitive capacity and quality of life was investigated. The hippocampal volume was measured using magnetic resonance imaging, and the ratios of the major metabolites were calculated using proton magnetic resonance spectroscopy. Cognitive testing revealed significant improvements in visuospatial cognitive function after rhGH. The hippocampal volume remained unchanged. In the right hippocampus, the N-acetylaspartate/creatine ratio (reflecting nerve cell function) was initially low but increased significantly during rhGH treatment, as did subjective cognitive, physical and emotional functioning. This case report indicates that rhGH replacement therapy could improve cognitive behaviour and well-being, as well as hippocampal metabolism and functioning in opioid-treated patients with chronic pain. The idea that GH could affect brain function and repair disabilities induced by long-term exposure to opioid analgesia is supported.

Growth hormone regulates the sensitization of developing peripheral nociceptors during cutaneous inflammation

“…Although future studies would be needed to confirm, this may suggest that the link to IGF-1 levels and the effectiveness of a GH therapy may be specific to widespread muscle pain disorders in adults and not neonatal inflammatory pain states. Nevertheless, our results show GH has profound effects on injury responses during postnatal development, suggesting that a short course of low dose GH replacement therapy may eventually be used as an effective pharmacological treatment strategy for neonatal pain that does not cause unwanted side effects typically seen with extended GH delivery in humans [2,53]. As neonatal injury is known to alter primary afferent function [24] which can reorganize the developing DH if initiated at early ages [68], this strategy may also mitigate the long-term consequences of early life insult on adult nociceptive processing [14,68].…”

Brain Recovery after a Plane Crash: Treatment with Growth Hormone (GH) and Neurorehabilitation: A Case Report

“…According to this evidence, it is likely that GH may facilitate the proliferation, differentiation and survival of new neurons in response to brain injury. To date, only few studies in humans explore such a possibility indicating a positive effect for GH treatment together with specific neurorehabilitation [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]; but all patients in these studies had GH deficiency, and only one study [ 8 ] describes that GH administration, together with rehabilitation, may be useful for the recovery of TBI patients without GHD.…”

“…The hypothesis that GH and insulin-like growth factor 1 (IGF-I) play a role on brain repair after an injury was postulated years ago [ 16 , 17 , 18 , 19 ], and a number of studies from our group and others demonstrated this, both in GH-deficient (GHD) [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] and non-GHD [ 8 , 29 ] patients with acquired brain injury.…”

Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy?

“…Brain damage provoked during delivery was treated with GH in a 10-year-old girl, resulting in a significant improvement in cognitive function [ 117 ]. In patients treated with opioids, GH improved hippocampal cognitive function [ 118 ]. This beneficial effect likely involves the downregulation of NMDA receptors and the prevention of opioid-related excitotoxicity [ 64 ].…”