Spinal Cord Injuries Containing Asymmetrical Damage in the Ventrolateral Funiculus Is Associated With a Higher Incidence of At-Level Allodynia

Abstract

Approximately 70% of male rats receiving severe T8 spinal contusions develop allodynia in T5-7 dermatomes (at-level) beginning two weeks post-injury. In contrast, rats having either complete transections or dorsal hemisections do not develop allodynia at-level following chronic spinal cord injury (SCI). In the present study, incomplete laceration and contusion injuries were made to test for neuroanatomical correlates between areas of white matter damage/sparing at the lesion epicenter and the presence/absence of allodynia. Following incomplete laceration lesions and six weeks of behavioral testing, histological reconstruction and analysis of the lesion epicenters revealed a significant difference (p<.001) in the amount of ventrolateral funiculus (VLF) asymmetry between rats showing pain-like responses evoked by touch (74.5% ± 8.4% side-to-side difference in VLF damage) versus those not responding to touch (11.3% ± 4.4% side-to-side difference in VLF damage). A five week mean allodynia score for each rat that incorporates a full range of forces that are all innocuous in intact controls revealed that the degree of hypersensitivity at level is related to the extent of VLF asymmetry post-SCI. No other damaged spinal white matter or gray matter area was correlated with sensitivity to touch. Similar findings were obtained for rats receiving T8 contusions, a more clinically relevant injury. These data suggest that different extents of damage/sparing between the two sides of VLF are likely a requisite for the development of allodynia after SCI.

Cell Cycle Activation Contributes to Increased Neuronal Activity in the Posterior Thalamic Nucleus and Associated Chronic Hyperesthesia after Rat Spinal Cord Contusion

“…To estimate the incidence of animals that developed SCI pain, we defined hyperalgesic states as decreases in withdrawal threshold that exceed 20 % of mean baseline values. Using this criterion, 63 % (10 of 16) of the animals developed SCI pain, a value similar to that reported in previous studies using similar approaches [17,59,60]. These values likely underestimate the extent and incidence of hyperesthesia because SCI animals had severe motor deficits (described below) that hinder their ability to withdraw from mechanical stimuli.…”

Effects of exercise training on urinary tract function after spinal cord injury

“…This impact produces a moderate to severe incomplete SCI. Procedures for SCI followed our previously published protocols (41,49,50,91). Briefly, animals were anesthetized with a mixture of ketamine (80 mg/kg) and xylazine [10 mg/kg intraperitoneally (ip)] and 0.1-ml supplemental doses were given ip as needed to maintain a deep surgical level of anesthesia.…”

“…The lesion site tissue was sectioned on a cryostat (Leica CM 1850) at 30-m-thickness and stained with Luxol fast blue and cresyl violet (Kluver-Barrera method) per established protocols (41,90). Spot Advanced software (Diagnostic Instruments, Sterling Heights, MI) and a Nikon E400 microscope were used to obtain measurements for quantification of the lesion epicenter (based on total lesion area) as previously described (41,91).…”

“…Spot Advanced software (Diagnostic Instruments, Sterling Heights, MI) and a Nikon E400 microscope were used to obtain measurements for quantification of the lesion epicenter (based on total lesion area) as previously described (41,91). The percent white matter sparing was determined by dividing the white matter remaining at the epicenter by the average area of white matter present in more intact sections.…”

Effects of Lateral Funiculus Sparing, Spinal Lesion Level, and Gender on Recovery of Bladder Voiding Reflexes and Hematuria in Rats

“…Sections were stained with the standard Luxol fast blue (LFB) and cresyl violet procedure (Klüver-Barrera stain 48 ), which consisted of deparaffinization in xylene, dehydration in ethanol, overnight immersion in warm 0.1% LFB, two cycles of lithium carbonate with ethanol/distilled water rinse/wash, and 6-min immersion in warm cresyl violet. Precise reconstruction drawings were made of the injured cord to confirm the exact and total extent of the damage along the length of the entire lesion (in addition to the epicenter) by an observer blinded to both the surgical procedure and behavioral results, 47,49 thereby reducing the possibility of underestimating the size of the lesion while also verifying that specific spared WM regions were continuous through the mid-thoracic spinal cord. Lesions were then grouped into specific categories, eliminating those from analysis that did not fit the lesion extent criteria.…”