ONTOGENY OF NEUROCHEMICAL MECHANISMS OF PAIN REACTIVITY

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DESCRIPTION Infants are capable of responding to painful stimulation, however, these responses and the physiological mechanisms mediating these responses continue to develop after birth. The experiments proposed here examine changes observed in the neurokinin and glutamate neurotransmitter systems, which are involved in the pain responses of adult animals. Mice lacking the NK1 receptor (NK1 knockout), mice lacking the neuropeptides neurokinin-A and substance P (preprotachykinin-A knockout), and wildtype controls are tested for responsivity on acute and tonic pain, allodynia and hyperalgesia to determine the functional role of the neurokinin system across development. Involvement of the glutamate NMDA receptor in pain reactivity across development is also examined by intrathecal administration of MK-801, an NMDA receptor antagonist, in wildtype animals. The development of the interaction between the neurokinin neurotransmitter system is characterized by assessing the effect of intrathecal administration of MK-801 in NK1 knockout and preprotachykinin-A knockout mice. Alterations in the synthesis and expression of neurokinin, CGRP, and glutamate peptides and receptors in the knockout mice are assessed across development using in situ hybridization and immunocytochemistry. Understanding changes in the neurotransmitter systems across development is important in understanding the pain response, and treatment of pain in infants.