Pain MechanismEffects of distal nerve injuries on dorsal-horn neurons and glia: Relationships between lesion size and mechanical hyperalgesia
Section snippets
Animal care and distal nerve injury (DNI) surgery
Male Sprague–Dawley rats (200–230 g, Charles River Laboratories, Wilmington, MA, USA) were housed in smooth-bottomed cages with free access to food and water. Rats were randomly assigned to undergo partial-DNI (n=32), total-DNI (n=28), or to serve as unoperated controls (n=8). Rats were rested for at least 48 h after arrival and then underwent 3 days of behavioral testing, the median of which defined the baseline value. All procedures were approved by the Institutional Animal Care and Use
Results
DNI rats appeared to ambulate and explore as much control rats, and their feeding was judged unimpaired because weight gain in both groups of DNI rats was similar to that of unoperated rats (P≥0.49). Neither autotomy nor tremors were detected in any rats. Some DNI rats developed sustained (tonic) abnormal postures of their ipsilesional hind paws, specifically lateral hind-paw-margin elevation and paw eversion, or plantar-flexion of all digits with ambulation on the volar surface of the digit.
Discussion
We generated a nerve injury that models the epidemiological characteristic of neuralgia, namely, that it does not always follow nerve injury. Most extant rodent models of neuralgia produce pain-behaviors in all or most lesioned animals. While efficient for preclinical testing, this precludes exploration of which post-lesioning changes are specifically associated with pain development. Seven days after our tibial-nerve lesions, 63% of rats had mechanical allodynia; 29% had prolonged withdrawal
Conclusion
In summary, this study demonstrates that partial axotomies of one distal nerve can be as effective as or more effective than total axotomies at producing long-lasting intraterritorial and extraterritorial hind-paw mechanical and thermal pain behaviors. A smaller, partial lesion was as effective as total axotomy at causing trans-synaptic and widespread effects on GABAergic interneurons and astrocytes in the dorsal-horn. This cellular “magnification” appears to develop within the dorsal horn
Acknowledgments
The technical assistance of Li Zheng, Ralph Gott, YangFeng Li, and statistical support of Dr. Yuchiao Chang are gratefully acknowledged. Supported in part by the Public Health Service (R01NS42866, K24NS059892, P30 EY 12196), the Beatrice and Roy Backus Foundation, and the RSDSA Rachel Tobias Young Investigator Award. Presented to the Society for Neuroscience in abstract form.
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2018, The Lancet NeurologyCitation Excerpt :The molecular markers for this inhibitory pathway are the vesicular glutamate transporter VGLUT2106 on peripheral neurons and the transcription factor gene Bhlhb5 on spinal neurons that release GABA and dynorphin to desensitise spinothalamic tract itch neurons.107 Ablation of glycinergic interneurons in the deeper laminae that inhibit itch and pain has been linked to NI in animal models, in vivo and ex vivo.108,109 Input from low threshold mechanoreceptors can also inhibit spinal itch processing via interneurons expressing neuropeptide Y.110 Itch and pain are presumably inhibited by light stroking and firm pressure, and might explain why tight garments or wraps sometimes improve NI and NP, in addition to physically blocking the scratching.
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