There is a range of available pharmacological therapies for the treatment of migraine, including opioids. Most of the opioids currently used in clinical practice are predominantly mu-agonists, although their use in migraine is controversial- they have relatively low efficacy, significant abuse potential, and an association with new-onset chronic migraine. Delta-opioid receptors (DORs) may avoid these adverse effects, and are expressed in a number of regions involved in headache, including trigeminal and dorsal root ganglia, trigeminal nucleus caudalis, and the cortex. The objective of this study was to investigate the effectiveness of DOR agonists in the treatment of acute migraine. We searched the PubMed database for all studies. We included pre-clinical, in vivo studies (between 2012-2022) that modelled effects of delta-opioids on migraine states. Four studies met the selection criteria. Their results demonstrated that DOR agonists inhibited migraine-associated endpoints, including cortical spreading depression, nitroglycerin (a known human migraine trigger) evoked hyperalgesia and aversive state. Risk of bias, assessed by both authors within the Cochrane ‘risk of bias’ framework, was high or unclear in each of the studies, due to a lack of blinding in allocation and outcome assessment. Additionally, each study used different DOR agonist ligands (SNC80, ARM390 and JNJ20788560), making integration of results difficult. Our interpretation of the evidence is that DORs are a promising target for acute migraine therapy. However, further investigations are required to evaluate for adverse effects of the various DOR agonist ligands before transition to clinical trials.
References
Amynah, A et al (2010) Ligand-directed trafficking of the delta-opioid receptor in vivo: two paths toward analgesic tolerance Journal of Neuroscience 30(49) pp. 16459-16468
Befort, K et al (2011). The Delta Opioid Receptor: An Evolving Target for the Treatment of Brain Disorders. Trends in Pharmacological Sciences, 32(10), pp. 581-590
Bigal, M (2011) The Paradoxical Effects of Analgesics and the Development of Chronic Migraine 69 (3), pp. 544-551
Buse, D et al (2011) Opioid use and dependence among persons with migraine: results of AMPP study American Headache Society 30(49)
Costa, C (2013). Cortical Spreading Depression as a Target for Anti-migraine Agents. The Journal of Headache and Pain 14, pp. 1129-118
DuPen, A et al (2007). Mechanisms of Opioid-Induced Tolerance and Hyperalgesia. Pain Management 8(3): pp. 113-121
Marcelo, E et al (2004). Opioid therapy and headache, a cause and cure. Neurology, 62(10), pp. 1662-1665
Negus, S et al (2011). Effects of the Delta Opioid Receptor Agonist SNC80 on Pain-related Depression of Intra-Cranial Self-Stimulation in rats. The Journal of Pain 13(4): pp. 317-327
Pradhan, A et al (2014). Delta-opioid receptor agonists inhibit migraine-related hyperalgesia, aversive state and cortical spreading depression in mice. British Journal of Pharmacology 171, pp. 2375-2384
Saitoh, A et al (2004) Potential anxiolytic and antidepressant-like activities of SNC80, a selective delta-opioid agonist, in behavioural models in rodents Journal of Pharmacological sciences 95, pp. 374-380
Steiner, T et al (2013) Migraine: the seventh disabler. Journal of Headache and Pain 14(1), pp. 1186-1229