Modulation of sensitized C-fibers by adrenergic stimulation in human neuropathic pain

The chronic constriction injury model is widely used in studying mechanisms of neuropathic pain. In this model neuropathic pain can be influenced by sympathetic interventions. It is assumed that similar mechanisms as in animals are responsible for pain arising from nerve entrapment syndromes in humans. The aim of the present study was to investigate if in patients with nerve entrapment nociceptive afferents can be modulated by adrenergic stimulation.

Twenty patients with pain due to a unilateral entrapment of the median nerve and 10 controls were included in the study. Spontaneous pain, mechanical and thermal evoked pain were assessed within the innervation territory of the lesioned nerve and the corresponding contralateral segment in patients and on the right hand side in healthy volunteers. The examinations were performed at baseline, during whole body cooling (sympathetic activation) and whole body warming (sympathetic inhibition), and after norepinephrine iontophoresis.

All patients reported spontaneous pain. Mechanical allodynia, punctate hyperalgesia and cold allodynia was not found. According to side-to-side differences in heat pain thresholds, patients were separated in patients with (n=10) and without (n=10) heat hyperalgesia. Adrenergic stimulation did not induce or enhance spontaneous or mechanical evoked pain in any patient or control subject. However in patients with pre-existing heat hyperalgesia sympathetic stimulation aggravated heat hyperalgesia significantly. Further in these patients the decrease in heat pain thresholds observed after norepinephrine iontophoresis was significantly higher compared to patients without pre-existing heat hyperalgesia.

Sympathetic-afferent interaction does not play a major role in pain generation due to nerve entrapment. Nevertheless in a subgroup of patients nociceptive afferents show sensitivity to physiological and pharmacological sympathetic stimulation. This finding is important because it emphasises that despite there is no clinical detectable effect on pain sympathetic afferent interaction can be found.