Changes in GABA and GABA_B receptor expressions are involved in neuropathy in the rat cuneate nucleus following median nerve transection

Abstract

This study examined the relationship between changes in GABA transmission and behavioral abnormalities after median nerve transection. Following unilateral median nerve transection, the percentage of GABA-like immunoreactive neurons in the cuneate nucleus and that of GABA(B) receptor-like immunoreactive neurons in the dorsal root ganglion in the injured side decreased and reached a nadir at 4 weeks after median nerve transection. Four weeks after bilateral median nerve transection and intraperitoneal application with saline, baclofen (2 mg kg⁻¹), or phaclofen (2 mg kg⁻¹) before unilateral electrical stimulation of the injured median nerve, we investigated the level of neuropeptide Y release and c-Fos expression in the stimulated side of the cuneate nucleus. The neuropeptide Y release level and the number of c-Fos-like immunoreactive neurons in the baclofen group were significantly attenuated, whereas those in the phaclofen group had increased compared to the saline group. These findings indicate that median nerve transection reduces GABA transmission, promoting injury-induced neuropeptide Y release and consequently evoking c-Fos expression in cuneate nucleus neurons. Furthermore, this study used the CatWalk method to assess behavioral abnormalities in rats following median nerve transection. These abnormalities were reversed by baclofen treatment. Overall, the results suggest that baclofen treatment block neuropeptide Y release, subsequently lessening c-Fos expression in cuneate neurons and consequently attenuating neuropathic signal transmission to the thalamus.

Validity and reliability of the CatWalk system as a static and dynamic gait analysis tool for the assessment of functional nerve recovery in small animal models

“…All reviewed parameters are listed in Table . Table contains all publications included in the parameter analysis of this review and further indicates which parameters were analyzed in each publication (Abada, Schreiber, & Ellenbroek, ; Baiguera et al., ; Balkaya, Kröber, Gertz, Peruzzaro, & Endres, ; Cao et al., ; Cendelín, Voller, & Vozeh, ; Chen, Tsai, Lin, et al., ; Cheng et al., ; Cho, Nguyen, Satkunendrarajah, Branch, & Fehlings, ; Chuang et al., ; Côté, Detloff, Wade, Lemay, & Houlé, ; Deumens, Jaken, Marcus, & Joosten, ; Deumens et al., , ; Encarnacion et al., ; Ferdinandusse et al., ; Gabriel, Marcus, Walenkamp, & Joosten, ; Gensel et al., ; Hausner et al., ; Hetze, Römer, Teufelhart, Meisel, & Engel, ; Hill, Brodak, & Bartlett Bunge, ; Hilton et al., ; Hoffmann et al., ; Jeong et al., ; Lee, McKeon, & Bellamkonda, ; Lin et al., ; Matsuura et al., ; Mountney, Leung, Pedersen, Shear, & Tortella, ; Neumann et al., ; Petrosyan et al., ; Schira et al., ; Sheu et al., ; Singh, Murray, & Houle, ; Sucher et al., ; Truin et al., ; Vandeputte et al., ; Vlamings et al., ; Wang et al., , ; Westin, Janssen, Sager, & Temel, ; Yamamoto, Okui, Tatebe, Shinohara, & Hirata, ). Here 22 out of 42 analyzed papers showed high reliability and validity of at least one parameter measured by the catwalk.…”

“…All reviewed parameters are listed in Table 1. Table 2 contains all publications included in the parameter analysis of this review and further indicates which parameters were analyzed in each publication (Abada, Schreiber, & Ellenbroek, 2013;Baiguera et al, 2012;Balkaya, Kröber, Gertz, Peruzzaro, & Endres, 2013;Cao et al, 2008;Cendelín, Voller, & Vozeh, 2010;Chen, Tsai, Lin, et al, 2012b;Cheng et al, 1997;Cho, Nguyen, Satkunendrarajah, Branch, & Fehlings, 2012;Chuang et al, 2010;Côté, Detloff, Wade, Lemay, & Houlé, 2012;Deumens, Jaken, Marcus, & Joosten, 2007;Deumens et al, 2006Deumens et al, , 2013Encarnacion et al, 2011;Ferdinandusse et al, 2008;Gabriel, Marcus, Walenkamp, & Joosten, 2009;Gensel et al, 2006;Hausner et al, 2012;Hetze, Römer, Teufelhart, Meisel, & Engel, 2012;Hill, Brodak, & Bartlett Bunge, 2012;Hilton et al, 2013;Hoffmann et al, 2010;Jeong et al, 2011;Lee, McKeon, & Bellamkonda, 2010;Lin et al, 2010;Matsuura et al, 2013;Mountney, Leung, Pedersen, Shear, & Tortella, 2013;Neumann et al, 2009;Petrosyan et al, 2013;Schira et al, 2012;Sheu et al, 2012;Singh, Murray, & Houle, 2011;Sucher et al, 2010;…”

Evaluation of Functional Recovery in Rats After Median Nerve Resection and Autograft Repair Using Computerized Gait Analysis

“…Interestingly, gait analysis did not show maximal alterations from baseline at WPO4 but WPO2 instead, indicating that immunohistochemical findings might follow a different course than behavioral changes following PNI. This is underpinned by the findings of (Chen et al, 2012a) who have reported a maximum decrement of Mean Paw Print Intensity at DPO3. Although these authors performed median nerve ligation, which is known to induce painful neuropathy (Kim and Chung, 1992;Kim et al, 1997) in addition to nerve transection, they found the same spatiotemporal expression patterns of neuropeptide Y and c-Fos as reported in the aforementioned studies.…”

“…This contrasts immunohistochemical (Lue et al, 2002;Tsai et al, 2004Tsai et al, , 2009Yeh et al, 2008;Lin et al, 2012) and behavioral studies (Chen et al, 2012a,b;Shaikh et al, 2016) of neuropathic pain following median nerve neurotmesis. Chen et al (2012a) have reported a 20% decrease in Mean Paw Print Intensity at DPO3 following 2-mm median nerve resection and concomitant ligation, which recovered to >90% of baseline at DPO7. The same authors have reported significant alterations of neuropeptide Y and c-Fos expression (Chen et al, 2012b), which are additional indicators of neuropathic pain, following the aforementioned injury pattern.…”

The Median Nerve Injury Model in Pre-clinical Research – A Critical Review on Benefits and Limitations

“…The more pressure is exerted, the larger the total area of skin–floor contact and thus the brighter the pixel. An appropriate software visualises the prints and calculates statistics related to print dimensions and the time and distance relationships between footfalls (Chen et al, 2012a,b).…”