Hyperalgesia due to nerve injury-role of peroxynitrite.

We carried out a partial ligation of the sciatic nerve in rats to induce nerve injury and neuropathic hyperalgesia. We showed that nitrotyrosine, a marker of peroxynitrite activity, was formed after partial nerve injury. Double-labelling immunohistochemistry showed that nitrotyrosine-immunoreactive cells were mainly macrophages and Schwann cells. Daily treatment with uric acid, a scavenger of peroxynitrite, decreased nitrotyrosine formation in the injured sciatic nerve, and produced concomitant alleviation of thermal hyperalgesia and Wallerian degeneration. These results provide the first evidence that peroxynitrite is formed after partial nerve injury, and contributes to the initiation of thermal hyperalgesia and Wallerian degeneration. We hypothesize that uric acid alleviates hyperalgesia and Wallerian degeneration by inhibiting oxidative damage caused by peroxynitrite and possibly also by decreasing the production of other inflammatory mediators such as prostaglandins.

Zinc alleviates thermal hyperalgesia due to partial nerve injury.

Zinc has recently been shown to alleviate inflammatory hyperalgesia. In the present study, we showed that intrathecal, intraplantar or systemic injection of zinc chloride significantly relieved thermal hyperalgesia in rats with sciatic nerve injury. Alleviation of thermal hyperalgesia was dose dependent in each case, although higher doses were required for i.p. injections (ED50 = 13.6 nmole) than for intrathecal (ED50 = 0.05 nmole) or intraplantar injections (ED50 = 0.3 nmole). Neither intrathecal nor intraplantar zinc chloride influenced thermal nociception in normal rats without nerve injury. The results provide the first evidence that zinc alleviates neuropathic hyperalgesia.

Neurons in the dorsal column nuclei of the rat respond to stimulation of neck mechanoreceptors and project to the thalamus.

Electrophysiological recordings were made from neurons in the dorsal column nuclei which were activated by stimulation of muscle and cutaneous receptors in the neck of the rat. 222 units were studied, 158 (71%) of which responded to activation of cutaneous mechanoreceptors while 64 (29%) were activated by muscle receptors. The response patterns of 12 neurons with input from receptors in neck muscles were tested more fully. Their response patterns strongly suggested that 6 were activated by muscle spindle afferents while the other 6 were activated by Golgi tendon organ afferents. 18 (8%) of the neck-responsive neurons in the medulla were shown to project rostrally to the thalamus.

Spinothalamic and propriospinal neurones in the upper cervical cord of the rat: terminations of primary afferent fibres on soma and primary dendrites.

Experiments were performed on rats to determine whether primary afferents from the upper cervical region terminate directly on spinothalamic and propriospinal neurones. The central terminations of primary afferents from the upper cervical region were identified by diffusely filling their axons with horseradish peroxidase. Spinothalamic neurones or propriospinal neurones were identified in the same experimental animals by using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Approximately 3-11% of spinothalamic cells in laminae 4-6 of spinal segments C2-4 received apparent synaptic contacts from primary afferents on the soma or primary dendrites. Approximately 18-36% of propriospinal neurones with axons descending to lower thoracic or lumbar levels received apparent synaptic contacts on the soma or primary dendrites. These data provide anatomical evidence that spinothalamic and long propriospinal neurones in the upper cervical cord are excited directly by primary afferents. The data also help to clarify the neural circuitry underlying somatic sensation and reflex movements evoked by neck receptors.

The medullary relay from neck receptors to somatosensory thalamus in the rat: a neuroanatomical study.

Experiments were performed on rats to determine the location of thalamic projecting neurones in the medulla which receive direct contacts from neck primary afferents. The medullary terminations of primary afferents from the cervical region were identified by silver staining their degenerating terminals, diffusely filling their axons with horseradish peroxidase (HRP), or reacting for transganglionically transported HRP applied to muscle or cutaneous nerves. Neurones projecting to the ventrobasal thalamus were identified in the same experimental animals by using retrograde transport of HRP or Fluoro-Gold. En passant swellings or terminals of neck primary afferents were found in the vicinity of neurones projecting to the thalamus in the dorsolateral part of the rostral cuneate nucleus, the ventral aspect of the external cuneate nucleus, and the border zone between the two. Terminals of neck afferents and retrogradely labelled cells also coincided in nucleus x. Putative synaptic contacts were found in the region between the dorsolateral part of the rostral cuneate nucleus and ventromedial external cuneate nucleus. Cutaneous afferents from the neck were associated with thalamic projecting cells located along the dorsolateral border of the rostral cuneate nucleus, and afferents from neck muscles were associated with thalamic projecting cells in the caudal third of the external cuneate nucleus and in nucleus x.