Behavioral evidence of trigeminal neuropathic pain following chronic constriction injury to the rat's infraorbital nerve

Abstract

Video recordings of free behavior and responses to mechanical facial stimulation were analyzed to assess whether chronic constriction injury (CCI) to the rat's infraorbital nerve (IoN) results in behavioral alterations indicative of neuropathic pain. A unilateral CCI was produced by placing loose chromic gut ligatures around the IoN. After CCI to the IoN, rats exhibited changes in both non-evoked and evoked behavior. Behavioral changes developed in two phases. Early after CCI (postoperative days 1–15), rats showed increased face-grooming activity with face-wash strokes directed to the injured nerve territory, while the responsiveness to stimulation of this area was decreased. Later after CCI (postoperative days 15–130), the prevalence of asymmetric face grooming was reduced but remained significantly increased compared to control rats. The early hyporesponsiveness was abruptly replaced by an extreme hyperresponsiveness: all stimulus intensities applied to the injured nerve territory evoked the “maximal” response (brisk head withdrawal, avoidance behavior plus directed face grooming). This response was never observed in control rats. Concurrently, IoN ligation rats showed a limited increase in the responsiveness to stimulation of the contralateral IoN territory, and around postoperative days 30–40 the responsiveness to stimulation of facial areas outside the IoN territories also increased. The hyperresponsiveness to stimulation of the ligated IoN territory slightly decreased from 60 d postoperative. Throughout the study, IoN ligation rats showed decreased exploratory behavior, displayed more freezing-like behavior, had a slower body weight gain, and a higher defecation rate, compared to control rats. The behavioral alterations observed after CCI to the IoN are indicative of severe sensory disturbances within the territory of the injured nerve: mechanical allodynia develops after a period of relative hypo- /anesthesia during which behavioral signs of recurrent spontaneous, aversive (possibly painful) sensations (paresthesias/dysesthesias) are maximal.

Differential Implication of Proinflammatory Cytokine Interleukin-6 in the Development of Cephalic versus Extracephalic Neuropathic Pain in Rats

“…The marked decrease of nociceptive threshold occurring 6 h after surgery in both IoN-CCI and sham rats probably corresponded to a traumatic response, because this allodynia-like behavior gradually disappeared in sham rats, as reported previously by others (Idanpaan-Heikkila and Guilbaud, 1999). The relative hyposensitivity of IoN-CCI rats observed at postoperative days 1 and 7 before the dramatic increase of responsiveness to mechanical stimulation is in line with previous data published on this model (Vos et al, 1994).…”

“…Unilateral chronic constriction injury to the infraorbital nerve was performed under direct visual control using a Zeiss microscope (10 -25ϫ) essentially as described by Vos et al (1994). Briefly, the head was fixed in a HorsleyClarke stereotaxic frame, and a midline scalp incision was made, exposing skull and nasal bone.…”

“…The orbital contents were gently deflected to give access to the infraorbital nerve, which was dissected free at its most rostral extent in the orbital cavity, just caudal to the infraorbital foramen. Only 5 mm of the nerve could be freed (Vos et al, 1994), providing the space for placement of two chromic catgut (5-0) ligations tied loosely (with ϳ2 mm spacing) around it. To obtain the desired degree of constriction, the criterion formulated by Bennett and Xie (1988) was used: the ligations reduced the diameter of the nerve by a just noticeable amount and retarded, but did not interrupt, the epineural circulation.…”

“…Behavioral nociceptive response consisted of (1) a brisk withdrawal reaction: the rat pulls briskly backward; (2) an escape/attack: the rat avoids additional contact with the filament either passively by moving its body away from the stimulating object to assume a crouching position against cage wall, sometimes with the head buried under the body, or actively by attacking the stimulating object, making biting and grabbing movements; or (3) asymmetric face grooming: the rat displays an uninterrupted series of at least three face-wash strokes directed to the stimulated facial area, often preceded by the brisk withdrawal reaction. The latter responses represent the highest scores in the rank-ordered response scoring system initially described by Vos et al (1994). The minimal force filament causing at least one among these responses (to at least two of the three on each side) allowed determination of the mechanical response threshold.…”

Viral Vector-based Gene Transfer for Treatment of Chronic Pain

“…57 We reported that HSV-mediated expression of proenkephalin reduces pain-related behavior in a rodent model of pain caused by cancer in bone. 58 In a rat model of trigeminal neuropathic pain which shares numerous similarities with human trigeminal neuralgia and trigeminal neuropathic pain, 59 Pohl and coworkers demonstrated that transgene-derived met-enkephalin significantly reduced mechanical hyperresponsiveness. 60 This antiallodynic effect was reversed by both the opioid receptor antagonist naloxone and the peripherally acting antagonist naloxone methiodide.…”