Neonatal hind-paw injury disrupts acquisition of an instrumental response in adult spinal rats.

The present study was designed to evaluate the impact of neonatal injury on adult spinal plasticity in rats. Subjects were randomly assigned to 1 of 4 experimental conditions: (a) hind-paw injury at Postnatal Day (PD) 2, (b) hind-paw injury at PD 5, (c) anesthesia exposure only on PD 2, or (d) anesthesia exposure only on PD 5. Subjects receiving a unilateral neonatal hind-paw injury showed decreased mechanical threshold (hyperalgesia) on the previously injured hind paw throughout development. This decrease in threshold survived spinal transection (at T2) at 12 weeks of age. Injured subjects also showed significant impairment in a spinal instrumental learning task performed by the previously injured hind paw. This disruption of learning indicates a disruption of spinal plasticity that may be due to induction of long-term changes in nociceptive processing within the spinal cord.

Lipopolysaccharide induces a spinal learning deficit that is blocked by IL-1 receptor antagonism.

Previous studies have shown that spinal neurons are capable of supporting a form of instrumental conditioning. Subjects receiving a spinal transection will learn to maintain a flexion response after exposure to shock contingent on leg position. In contrast, subjects receiving shock irrespective of leg position will not show increased flexion duration. Activation of the immune system has deleterious effects on learning in intact animals, but the impact of immune system activation on learning spinal animals is not known. We found that a large dose of i.p. LPS (1.0mg/kg) significantly disrupted the acquisition of the instrumental flexion response. The LPS-induced learning deficit was not prevented by preexposure to contingent shock (i.e. immunization) (Experiment 2). Co-administration of the iNOS inhibitor L-NIL (0.1, 1.0 and 10.0 microg/microL) failed to block the deficit (Experiment 3). Co-administration of an IL-1 receptor antagonist (r-metHuIL-1ra [10.0, 30.0 and 100.0 microg/microL) prevented the LPS-induced learning deficit when given in a dose of 100.0 microg/microL(i.t.) only (Experiment 4). Findings indicate a role for spinal IL-1 in the decreased plasticity following LPS administration.