Is there a place for beta-mimetics in clinical management of neuropathic pain? Salbutamol therapy in six cases.

THE Adrenergic system, because of its reported implication in pain mechanisms, may be a potential target for chronic pain treatment. A genetic polymorphism of catechol-O-methyltransferase, an enzyme that metabolizes catecholamines, is related with higher pain perception and persistent pain conditions because patients with higher pain sensitivity are more likely to develop chronic pain conditions. Moreover, catechol-O-methyltransferase inhibition increases pain sensitivity through augmented catecholamines and activation of -adrenergic ( -AR) receptors. Furthermore, a polymorphism of 2-adrenoceptors ( 2-AR) has been associated with the risk for developing musculoskeletal pain disorders. In agreement, clinical studies reported that -AR antagonists were effective in chronic musculoskeletal pain conditions, such as fibromyalgia or temporomandibular disorder. This effect on myalgic pain was observed in patients with altered sympathetic nervous function. In addition to musculoskeletal pain disorders, neuropathic pain is another major type of chronic pain. Neuropathic pain arises as a direct consequence of a lesion or a disease affecting the somatosensory system. The prevalence of neuropathic pain has been reported to be around 6.9 and 8.2% in two large prevalence studies, and the annual incidence rate was estimated at 1%. Even though patients with neuropathic symptoms are rather frequent, neuropathic pain is often challenging to treat and is generally resistant to commonly used therapeutics. Treatment difficulties may be due to various underlying pathophysiologic mechanisms. Indeed, neuropathic pain can be initiated not only by various diseases such as diabetes or cancer but also by trauma, postsurgical injuries, or drug treatment of cancer or human immunodeficiency virus infection. Currently, antidepressants are one of the first-line treatment options in neuropathic pain management. These drugs are indirect adrenergic agonists because they act through the blockade of aminergic reuptake sites and thus increase endogenous levels of noradrenaline. Recent studies on the action mechanisms of antidepressants in neuropathic pain revealed the critical role played by 2-AR. 13,14 The absence or blockade of 2-ARs suppresses the antiallodynic effects of a chronic antidepressant treatment in a neuropathic pain model. Interestingly, preclinical studies have also reported that the chronic direct stimulation of 2-ARs by agonists can alleviate neuropathic pain symptoms in a murine neuropathic pain model, whereas a -AR antagonist had no effect. Thus, these findings differ from what was observed in musculoskeletal pain. In this report, we show that the use of salbutamol, a shortacting 2-AR agonist, provided satisfying symptom management in six patients with severe neuropathic pain resistant to previous therapy.