Heat nociception is severely reduced in a mutant mouse deficient for the L1 adhesion molecule.

Recent findings indicate that the spatial organization of the spinal nociceptive reflex system is adjusted postnatally through experience-dependent mechanisms. The cellular and molecular mechanisms underlying this tuning are not known. Because the adhesion molecule L1 is known to play an important role in neural development and synaptic plasticity, we studied the nociceptive withdrawal reflexes in awake adult mutant mice deficient in L1. Withdrawal reflexes were elicited by a CO(2) laser (heat stimulation) and von Frey monofilaments (tactile stimulation). L1-deficient mice (n=10) had an abnormally high nociceptive heat-reflex threshold compared with wild-type mice (n=11), except for the nose. Other behavioral signs of heat pain, such as vocalization, were either absent or strongly reduced in L1-deficient mice. Tactile thresholds for withdrawal reflexes were increased in L1-deficient mice when compared with wild-types except for the tail. By contrast, the spatial organization of the withdrawal reflexes appeared normal indicating that the L1 adhesion molecule is not essential for the spatial adjustments of reflex connections during development. The termination patterns of thin primary afferent fibers in the superficial dorsal horn, visualized using intra-plantar injections of WGA-HRP, were normal, suggesting that decreased nociceptive heat sensitivity in L1-deficient mice is mainly due to altered central processing. In view of the known interactions between L1 and some of the NMDA-receptor subtypes, and the prominent role of NMDA receptors in nociception and plasticity, it is conceivable that the hypoalgesia seen in L1 mutants is due, in part, to disturbed NMDA-receptor function.