Peripheral nerve injury sensitizes the response to visceral distension but not its inhibition by the antidepressant milnacipran.
BACKGROUND
Manipulations that cause hypersensitivity to visceral stimuli have been shown to also result in hypersensitivity to somatic stimuli coming from convergent dermatomes, but the converse has not been examined. The authors tested whether lumbar spinal nerve ligation in rats, a common model of neuropathic pain that results in hypersensitivity to somatic stimuli, also leads to hypersensitivity to visceral stimuli coming from convergent dermatomes and whether pharmacology of inhibition differed between these two sensory modalities.


METHODS
Female Sprague-Dawley rats were anesthetized, and the left L5 and L6 spinal nerves were ligated. Animals received either intrathecal saline or milnacipran (0.1-3 microg), and withdrawal thresholds to mechanical testing in the left hind paw, using von Frey filaments, and visceral testing, using balloon colorectal distension, were determined.


RESULTS
Nerve ligation resulted in decreases in threshold to withdrawal to somatic mechanical stimulation (from 13 +/- 1.8 g to 2.7 +/- 0.7 g) and also in decreases in threshold to reflex response to visceral stimulation (from 60 mmHg to 40 mmHg). Intrathecal milnacipran increased withdrawal threshold to somatic stimulation in a dose-dependent manner but failed to alter the response to noxious visceral stimulation.


CONCLUSIONS
Injury of nerves innervating somatic structures enhances nociception from stimulation of viscera with convergent input from nearby dermatomes, suggesting that somatic neuropathic pain could be accompanied by an increased likelihood of visceral pain. Lack of efficacy of the antidepressant milnacipran against visceral stimuli suggests that visceral hypersensitivity may not share the same pharmacology of inhibition as somatic hypersensitivity after nerve injury.
Shin
Sang-Wook
SW
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Eisenach
James C
JC
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002404:Catheterization; D003521:Cyclopropanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005260:Female; D007278:Injections, Spinal; D008026:Ligation; D000078764:Milnacipran; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D059348:Peripheral Nerve Injuries; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000293:injuries / Q000473:pathology
D000928:Antidepressive Agents; D003521:Cyclopropanes; D000639:Amitriptyline; D000078764:Milnacipran