title: A new model of nerve injury in the rat reveals a role of Regulator of G protein Signaling 4 in tactile hypersensitivity.
abstract: Tactile hypersensitivity is one of the most debilitating symptoms of neuropathic pain syndromes. Clinical studies have suggested that its presence at early postoperative stages may predict chronic (neuropathic) pain after surgery. Currently available animal models are typically associated with consistent tactile hypersensitivity and are therefore limited to distinguish between mechanisms that underlie tactile hypersensitivity as opposed to mechanisms that protect against it. In this study we have modified the rat model of spared nerve injury, restricting the surgical lesion to a single peripheral branch of the sciatic nerve. This modification reduced the prevalence of tactile hypersensitivity from nearly 100% to approximately 50%. With this model, we here also demonstrated that the Regulator of G protein Signaling 4 (RGS4) was specifically up-regulated in the lumbar dorsal root ganglia and dorsal horn of rats developing tactile hypersensitivity. Intrathecal delivery of the RGS4 inhibitor CCG63802 was found to reverse tactile hypersensitivity for a 1h period. Moreover, tactile hypersensitivity after modified spared nerve injury was most frequently persistent for at least four weeks and associated with higher reactivity of glial cells in the lumbar dorsal horn. Based on these data we suggest that this new animal model of nerve injury represents an asset in understanding divergent neuropathic pain outcomes, so far unravelling a role of RGS4 in tactile hypersensitivity. Whether this model also holds promise in the study of the transition from acute to chronic pain will have to be seen in future investigations.
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Av. Hippocrate 54, Brussels, Belgium; Neuroscience Department, International School for Advanced Studies (SISSA), via Bonomea 265, Trieste, TS, Italy; SPINAL (Spinal Person Injury Neurorehabilitation Applied Laboratory), Istituto di Medicina Fisica e Riabilitazione (IMFR), via Gervasutta 48, Udine (UD), Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Taccola
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Av. Hippocrate 54, Brussels, Belgium.
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Doyen
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Av. Hippocrate 54, Brussels, Belgium.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Damblon
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Av. Hippocrate 54, Brussels, Belgium; Neuroscience Department, International School for Advanced Studies (SISSA), via Bonomea 265, Trieste, TS, Italy; SPINAL (Spinal Person Injury Neurorehabilitation Applied Laboratory), Istituto di Medicina Fisica e Riabilitazione (IMFR), via Gervasutta 48, Udine (UD), Italy.
authors.forename: Nejada
authors.initials: N
authors.lastname: Dingu
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Av. Hippocrate 54, Brussels, Belgium.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Ballarin
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Av. Hippocrate 54, Brussels, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Steyaert
authors.affiliation: Louvain Drug Research Institute, Av. Mounier 73, Brussels and Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium.
authors.forename: Anne des
authors.initials: AD
authors.lastname: Rieux
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Av. Hippocrate 54, Brussels, Belgium.
authors.forename: Patrice
authors.initials: P
authors.lastname: Forget
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Av. Hippocrate 54, Brussels, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hermans
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Av. Hippocrate 54, Brussels, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bosier
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Av. Hippocrate 54, Brussels, Belgium. Electronic address: ronald.deumens@uclouvain.be.
authors.forename: Ronald
authors.initials: R
authors.lastname: Deumens
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D001703:Biophysics; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008840:Microfilament Proteins / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000150:complications* / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D020710:RGS Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: C100745:Aif1 protein, rat; D052160:Benzothiazoles; C000618819:CCG63802; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D011743:Pyrimidines; D020710:RGS Proteins; D012333:RNA, Messenger; C098799:RGS4 protein
keywords: Allodynia; Animal model; Chronification; Glia; Neuropathic pain; RGS