Association of neural inflammation with hyperalgesia following spinal nerve ligation.
OBJECTIVE
To explain the variability in the behavioral response after spinal nerve ligation by investigating the relation between the development of neuropathic pain and the expression of inflammatory indicators, in dorsal root ganglia (DRG) and the spinal nerve.


METHODS
Ninety-six male Sprague-Dawley rats were randomly assigned to the modified spinal nerve ligation, sham, and control group. Testing for pain-related behavior identified rats that successfully developed neuropathic pain (responders) and those which did not (non-responders). The extent of neuroinflammation in the two groups was assessed by immunohistochemical staining of dorsal root ganglions glial fibrillary acid protein (GFAP), and rat C3 complement receptor (OX-42).


RESULTS
GFAP and OX-42 immunopositive cell density in the DRG and spinal nerve was significantly higher in hyperalgesic animals. DRG cell density was 3.96+/-0.68 cells/2500 microm2 in GFAP responders' group, compared with 2.76+/-0.75 cells/2500 microm2 in non-responders' group (Mann-whitney U test, Z=-3.956, P<0.001). OX-42 density was 7.71+/-1.03 cells/2500 microm2 in responders and 4.75+/-1.76 cells/2500 microm2 in non responders (Mann-whitney U test, Z=-2.572, P=0.01). Hyperalgesic behavior progressively increased during the testing period, although immunopositive cell density peaked on the fourth day post-injury and progressively decreased afterwards.


CONCLUSIONS
Our study suggests that inflammation has a decisive role in initiating neuropathic pain. Also, this study confirms that, for the sake of selecting appropriate subjects for mechanistic study, it is necessary to discriminate between experimental subjects that develop pain completely and those that do not.
Znaor
Ljubo
L
Department of Anatomy, Histology, and Embryology, Split University School of Medicine, Split, Croatia.
Lovrić
Sanja
S
Hogan
Quinn
Q
Sapunar
Damir
D
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D008026:Ligation / Q000009:adverse effects; D008297:Male; D009443:Neuritis / Q000209:etiology* / Q000503:physiopathology; D017288:Pain Threshold / Q000502:physiology; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013127:Spinal Nerves / Q000293:injuries* / Q000601:surgery; D018709:Statistics, Nonparametric