Loss of GABA-immunoreactivity in the spinal dorsal horn of rats with peripheral nerve injury and promotion of recovery by adrenal medullary grafts.

Abnormal pain-related behaviour that accompanies peripheral nerve injury may be the result of altered spinal neuronal function. The long-term loss of inhibitory function by GABA neurons in particular may be a mechanism by which abnormal neural hyperactivity occurs, leading to exaggerated sensory processing following nerve injury. In order to assess this, changes in spinal GABA immunoreactivity at several time points following constriction nerve injury were quantified in parallel with behavioural assessments of abnormal sensory responses to noxious and innocuous stimuli.

Alterations in rat spinal cord cGMP by peripheral nerve injury and adrenal medullary transplantation.

Adrenal medullary chromaffin cells implanted into the spinal subarachnoid space can reduce abnormal pain-related responses in chronic pain models. Persistent pain is thought to involve the activation of N-methyl-D-aspartate (NMDA) receptors and subsequent production of nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP). Changes in dorsal horn levels of cGMP in the rat were determined in conjunction with alterations in pain behaviors following peripheral nerve injury and adrenal medullary transplantation.

Expression of class II MHC molecules in the rat pineal gland during development and effects of treatment with carbon tetrachloride.

Cells expressing major histocompatibility complex (MHC) class II (Ia) antigen have been examined during the development of rat pineals and in the pineal gland of adult rats treated with carbon tetrachloride. Cells positive for MHC class II are first detected in the pineal gland of the 7-day-old rat. These positive cells increase in number gradually during development, MHC class II immunoreactivity reaching adult levels at 4 weeks after birth.

Adrenal medullary implants reduce transsynaptic degeneration in the spinal cord of rats following chronic constriction nerve injury.

Peripheral nerve injury causes abnormal sensory processing, possibly due in part to neuroplastic changes in the CNS. Following chronic constriction injury of the sciatic nerve, transsynaptic degeneration is suggested by the presence of "dark neurons" found in superficial laminae of spinal cord. Previous studies in our laboratory have shown that grafts of adrenal medullary cells into the spinal subarachnoid space can reduce abnormal pain due to peripheral nerve injury.

Modulation of NMDA receptor expression in the rat spinal cord by peripheral nerve injury and adrenal medullary grafting.

Excessive activation of N-methyl-D-aspartate (NMDA) receptors in the spinal cord consequent to peripheral injury has been implicated in the initiation of neuropathologic events leading to a state of chronic hyperexcitability and persistence of exaggerated sensory processing. In other CNS disease or injury states, NMDA-mediated neurotoxic damage is associated with a loss of NMDA receptors, and outcome may be improved by agents reducing NMDA activation. Previous findings in our laboratory have demonstrated that the transplantation of adrenal medullary tissue into the spinal subarachnoid space can alleviate sensory abnormalities and reduce the induction of a putative nitric oxide synthase consequent to peripheral nerve injury.

Morphological characterization of dorsal horn spinal neurons in rats with unilateral constriction nerve injury: a preliminary study.

A new animal model of neuropathic pain utilizing loose ligation of a peripheral nerve has been previously reported. In addition to displaying abnormal pain symptoms such as allodynia and hyperalgesia, physiologic and morphologic changes are seen in spinal cord dorsal horn neurons. Two weeks after ligation of the right common sciatic nerve, rat dorsal horn spinal cord neurons with signs of transsynaptic changes (dark neurons) were found on the side ipsilateral to the nerve injury.

Alleviation of neuropathic pain symptoms by xenogeneic chromaffin cell grafts in the spinal subarachnoid space.

Recent data have suggested that adrenal medullary tissue allografts in the spinal cord subarachnoid space, by releasing catecholamines and opioid peptides, attenuate responses to various acute noxious stimuli and chronic pain-related behaviors. However, the application of this approach is limited by the low availability of allogeneic donor material. Alternatively, chromaffin cells from xenogeneic sources such as the bovine adrenal medulla are plentiful and simple to extract.

Induction of spinal NADPH-diaphorase by nerve injury is attenuated by adrenal medullary transplants.

Persistent sensory abnormalities consequent to injury may involve prolonged neuroplastic changes in the spinal cord similar to those in long-term potentiation. Molecular markers, like the putative nitric oxide synthase, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), can be useful indicators of increased neuronal activity. Peripheral nerve injury markedly increased NADPH-d-labeling in sensory regions of the spinal cord, paralleling induction of abnormal pain (hyperalgesia).

Reduced pain-related behavior by adrenal medullary transplants in rats with experimental painful peripheral neuropathy.

Adrenal medullary transplants in the spinal subarachnoid space, by providing a continual source of opioid peptides and catecholamines, offer a potentially important adjunct in the management of chronic pain. While previous studies have shown that this approach is effective against high-intensity phasic stimuli, adrenal medullary implants need to be evaluated against long-term and abnormal pain syndromes before transplantation can be used for human chronic pain. Using a recently developed model of painful peripheral neuropathy, the effects of adrenal medullary chromaffin cells transplanted into the subarachnoid space was evaluated.

MK-801 blocks the development of thermal hyperalgesia in a rat model of experimental painful neuropathy.

Loose ligation of the sciatic nerve in the rat can produce behavioral signs of hyperalgesia in the hindpaw. This study examined the effect of an NMDA (N-methyl-D-aspartate) receptor antagonist (MK-801) on the development of hyperalgesia in this model. Rats received i.

Clonidine reduces substance P binding in rat spinal cord membrane preparation.

The effects of clonidine on substance P (SP) binding was investigated using rat brain and spinal cord membrane preparations preincubated with various concentrations of clonidine. [3H]SP specific binding in the spinal cord was significantly decreased with 10(-4) M clonidine, but no effect on binding was seen in the brain. Scatchard analysis of SP binding indicated that Bmax was significantly depressed without changing the affinity.