Short summary

This PhD project will test the effect of the beta-2-adrenergic drug terbutaline in patients with painful neuropathic pain. The first study will test the effect of terbutaline in comparison with the antidepressant drug imipramine and placebo in patients with painful polyneuropathy. A second study will test the effect of terbutaline in comparison with placebo in patients with focal peripheral neuropathic pain. The aim of these studies is to improve the treatment of neuropathic pain.

Rationale

Antidepressant drugs are first choice treatments of neuropathic pain, i.e. pain caused by diseases or lesions of the nervous system. Many patients experience unacceptable side effects with antidepressants and this limits their use in clinical practice. The pain relieving effect of these drugs has been linked to their effect on specific signal substances in the central nervous system which may enhance the endogenous pain suppressing neuronal networks. Recent experimental research has indicated that the analgesic action of antidepressants may be linked to a specific receptor (binding site) called the beta-2-adrenergic receptor which is activated by drugs with a widespread use in asthma and other chronic lung diseases. If this is the case these drugs used for lung diseases should provide a pain relief in neuropathic pain which is comparable the relief obtained with antidepressants. This PhD project will challenge this hypothesis in randomised, double-blinded, controlled, trials. One study will test the effect of the beta-2-adrenergic drug terbutaline in comparison with placebo and the antidepressant imipramine in 58 patients with painful generalised peripheral neuropathy. A second study will test if terbutaline relieve focal peripheral neuropathic pain more than placebo in a sample of 24 patients. The treatment periods with each treatment option will be of 5 weeks duration. Finally, responders to terbutalin across the two trials will be characterised with respect to pattern of pain symptoms and quantitative sensory examination abnormalities to search for clinical predictors of response. The goal of this project is to improve the treatment of neuropathic pain.

Description of the cohort

Study 1 will include adult patients with chronic painful polyneuropathy, and study 2 will include adult patients with focal peripheral neuropathic pain.

Data and biological material

Biological material: blood samples.

Data: each participant will be using a daily diary describing different pain symptoms, using NRS (numerical rating scale) for each pain symptom. Median score for each week (in baseline periods as well as treatment periods) will be calculated, where median score for total pain (NRS) will be the main effect variable. Patient´s global impression of change will also be used after each treatment period. Each participant will be examined with Quantitative Sensory Testing.

Collaborating researchers and departments

Danish Pain Research Center, Aarhus University Hospital