Evaluation of behavior and neuropeptide markers of pain in a simple, sciatic nerve-pinch pain model in rats

Abstract

Pathomechanisms of injured-nerve pain have not been fully elucidated. Radicular pain and chronic constriction injury models have been established; however, producing these models is complicated. A sciatic nervepinch injury is easy to produce but the reliability of this model for evaluating pain behavior has not been examined. The current study evaluated pain-related behavior and change in pain markers in the dorsal root ganglion (DRG) of rats in a simple, sciatic nerve-pinch injury model. In the model, the sciatic nerve was pinched for 2 s using forceps (n = 20), but not injured in sham-operated animals (n = 20). Mechanical and thermal hyperalgesia were measured every second day for 2 weeks using von Frey filaments and a Hargreaves device. Calcitonin gene-related peptide (CGRP), activating transcription factor-3 (ATF-3), phosphorylated p38 mitogen activated protein (Map) kinase (p-p38), and nuclear factor-kappa B (NF-jB; p65) expression in L5 DRGs were examined at 4 and 7 days after surgery using immunohistochemistry. The proportion of neurons immunoreactive for these markers was compared between the two groups. Mechanical (during 8 days) and thermal hyperalgesia (during 6 days) were found in the pinch group rats, but not in the sham-operated animals (p \ 0.05); however, hyperalgesia was not significant from days 10 to 14. CGRP, ATF-3, p-p38, and NF-jB expression in L5 DRGs was upregulated in the nerveinjured rats compared with the sham-operated rats (p \ 0.01). Our results indicate that a simple sciatic nerve pinch produced pain-related behavior. Upregulation of the pain-marker expression in the nerve-injury model suggested it could be used as a model of pain. However, it was not considered as suitable for long-term studies.

Temporal changes in MrgC expression after spinal nerve injury

“…4B right), as compared to that in sham-operated rats. This decreased and unchanged percentages of MrgC + neurons in IB4 and CGRP subpopulations of uninjured DRG neurons, respectively, may be due to phenotypic changes and increased expression of these markers in uninjured DRG after nerve injury (Hammond et al, 2004; Chao et al, 2008; Hirose et al, 2010; Nitzan-Luques et al, 2013). The IB4 signal was nearly completely lost, and the CGRP immunoreactivity was very weak and diffusive in the ipsilateral injured L5 DRG; hence their colocalization with MrgC could not be reliably determined.…”

“…Phenotypic changes in DRG neurons have been observed after inflammation and peripheral nerve injury (Xiao et al, 2002; Chao et al, 2008; Pernia-Andrade et al, 2009). Since nerve injury may change CGRP expression and IB4 binding in DRG neurons, and these changes are also different in injured and uninjured levels (Hammond et al, 2004; Chao et al, 2008; Hirose et al, 2010; Nitzan-Luques et al, 2013), a triple-immunofluorescence staining study is needed to determine the relative proportion and differential changes of MrgC expression in different subsets of DRG neurons after nerve injury.…”

Phenotypic change in trigeminal ganglion neurons associated with satellite cell activation via extracellular signal‐regulated kinase phosphorylation is involved in lingual neuropathic pain

“…CGRP expression is known to be reduced in dorsal root ganglion (DRG) neurons following nerve transection (Noguchi et al ., ; Nahin et al ., ). In contrast, the number of CGRP‐immunoreactive (IR) neurons is increased with peripheral inflammation (Ohtori et al ., ) or nerve crush in the DRG (Hirose et al ., ), and CGRP is also expressed in large DRG neurons after chronic constriction injury of the sciatic nerve (Miki et al ., ; Ohtori et al ., ). These results suggest that CGRP in primary afferent neurons is involved in modulation of excitability of DRG neurons associated with peripheral nerve injury.…”

Rapid and Delayed Effects of Pulsed Radiofrequency on Neuropathic Pain: Electrophysiological, Molecular, and Behavioral Evidence Supporting Long-Term Depression

“…ATF-3 is a member of the ATF/CREB transcription factor superfamily, and indicates stresses in DRG neurons after peripheral axonal injury or nonneural tissues following cellular destruction (51)(52)(53). ATF-3 was also suggested to E281 PRF Selectively Suppresses C-Fiber-Mediated Neuropathic Pain be involved in nociceptive development (54). Because the active zone of PRF was limited to a narrow range adjacent to the electrode tip (7,8,11), the severely affected tissue is theoretically the region in close contact with the electrode.…”