Spinal nerve ligation-induced neuropathy in the rat: sensory disorders and correlation between histology of the peripheral nerves.
We studied the effect of unilateral ligation of two spinal nerves on behavioral pain responses evoked by various types of cutaneous stimuli in the adult rat. Furthermore, we determined the effect of spinal nerve ligation on morphology of the peripheral nerves. The most consistent behavioral finding (83%) was a marked decrease in monofilament-induced hindlimb withdrawal thresholds (mechanical allodynia) ipsilateral to the spinal nerve ligation. This mechanical allodynia was observed as early as during the 1st post-operative day and it persisted up to 2 months (the maximum length of the observation period). In contrast, hyperalgesia to noxious mechanical stimulation (Randal-Sellitto test) was not observed in allodynic rats until the 3rd post-operative day. In a minority of rats (13%), spinal nerve ligation-induced mechanical hyperalgesia without a concomitant mechanical allodynia. There was no corresponding heat hyperalgesia in the injured hindlimb (hot water immersion-, radiant heat- or hot-plate-induced hindlimb withdrawal tests). In contrast, hypoalgesia to heat was observed on the 1st postoperative day, but not later. Neuropathological analysis of the peripheral nerves revealed a dramatic decrease in the number of myelinated nerve fibers distal to the spinal nerve ligation site. The results support the previous evidence indicating that ligation of spinal nerves induces a marked allodynia to mechanical stimulation. However, this mechanical allodynia may differentially dissociate from mechanical and thermal hyperalgesia at various post-operative time points. The marked mechanical allodynia together with a dramatic decrease in the number of myelinated nerve fibers is paradoxical, since the activation of myelinated nerve fibers by monofilaments produced abnormally strong behavioral responses. This paradox may be explained by spinal nerve ligation-induced amplification or disinhibition of tactile signals at central levels.
Röyttä
M
M
Department of Pathology, University of Turku, Finland.
Wei
H
H
Pertovaara
A
A
D000818:Animals; D006930:Hyperalgesia / Q000503:physiopathology; D008026:Ligation; D008297:Male; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D012678:Sensation Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012867:Skin / Q000503:physiopathology; D012881:Skin Temperature; D013127:Spinal Nerves / Q000473:pathology / Q000503:physiopathology*