An Adapted Chronic Constriction Injury of the Sciatic Nerve Produces Sensory, Affective, and Cognitive Impairments: A Peripheral Mononeuropathy Model for the Study of Comorbid Neuropsychiatric Disorders Associated with Neuropathic Pain in Rats.

BACKGROUND: Chronic constriction injury (CCI) is a model of neuropathic pain induced by four loose ligatures around the sciatic nerve. This work aimed to investigate the sensory, affective, cognitive, and motor changes induced by an adaptation of the CCI model by applying a single ligature around the sciatic nerve. METHODS: Mechanical allodynia was measured from day 1 to day 28 postsurgery by the von Frey test. The beam walking test (BWT) was conducted weekly until 28 days after surgery. Anxiety- and depression-like behaviors, and cognitive performance were assessed through the open field (OF), forced swimming (FS), and novel object recognition (NOR) tests, respectively, 21 days after surgery. RESULTS: The two CCI models, both Bennett and Xie's model (four ligatures of the sciatic nerve) and a modification of it (one ligature), induced mechanical allodynia, increased immobility in the FS, and reduced recognition index in the NOR. The exploratory behavior and time spent in the central part of the arena decreased, while the defensive behavior increased in the OF. The animals subjected to the two CCI models showed motor alterations in the BWT; however, autotomy was observed only in the group with four ligatures and not in the group with a single ligature. CONCLUSIONS: Overall these results demonstrate that our adapted CCI model, using a single ligature around the sciatic nerve, induces sensory, affective, cognitive, and motor alterations comparable to the CCI model with four ligatures without generating autotomy. This adaptation to the CCI model may therefore represent an appropriate and more easily performed model for inducing neuropathic pain and study underlying mechanisms and effective treatments.

Relevance of dorsomedial hypothalamus, dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal gray matter in the organization of freezing or oriented and non-oriented escape emotional behaviors.

Electrical stimulation of the periaqueductal gray matter and ventromedial hypothalamus in humans showed the involvement of both these structures in panic attacks. The aim of this work was to make clear the role of dorsal periaqueductal gray (dPAG) matter, dorsomedial hypothalamus (DMH) and the dorsomedial part of the ventromedial hypothalamus (dmVMH) in panic attack-like behaviors. DMH, dmVMH and dPAG of Wistar rats were treated with N-methyl- d-aspartic acid (NMDA) at different doses. The rodents were then kept in a polygonal arena with a burrow to record panic attack-like responses and oriented defensive behaviors. In dmVMH, 6nmol of NMDA elicited alertness, freezing and oriented escape. The same set of behaviors was elicited by DMH neurons when stimulated by 9nmol of NMDA. Treatment of dmVMH with 9nmol of NMDA elicited typical explosive behaviors followed by freezing and oriented behaviors. The stimulation of the dPAG with NMDA at different doses provoked alertness and freezing (1nmol) or alertness, freezing, tail twitching, explosive behavior and oriented escape (3nmol), and explosive behavior followed by long-lasting freezing (6nmol). These data suggest that mainly dPAG plays a role in panic attack-like behaviors that resemble panic syndrome in humans. However, hypothalamic nuclei like dmVMH that mainly elicits oriented escape, can also produce explosive reaction when stimulated with 9nmol NMDA, whereas, DMH plays a role in coordinating defensive behaviors.