Inflammatory pain reduces correlated activity in the dorsal column nuclei.

Persistent pain can result in sensitization of neurons in the spinal cord dorsal horn and produce physiological changes in sites such as the thalamus, that receive projections from the dorsal horn. Although the dorsal column nuclei receive both primary afferent input and projections from the dorsal horn, their participation in persistent pain states is relatively unexplored, perhaps because they play a limited role in acute, cutaneous nociception. We have used a model of inflammatory pain to examine the physiological properties of dorsal column nucleus neurons during persistent pain. We used this model in order to minimize direct damage to large myelinated primary afferents that project directly to the dorsal column nuclei. Inflammation was produced by injection of complete Freund's adjuvant into one hindpaw in rats, and neurons in the gracile nucleus were recorded 2-8 days later. Inflammation resulted in increased responsiveness to nociceptive (pinch) stimulation and increased incidence of afterdischarge firing 2-3 days after injection. Spontaneous activity was increased 6-8 days after injection. Inflammation decreased the strength of correlated firing in neuron pairs that shared common inputs, but did not affect the strength of monosynaptic interactions between neurons. These results suggest that the dorsal column nuclei can participate in persistent pain processes. Based on their anatomical connections, the dorsal column nuclei may contribute to thalamic changes during persistent pain as well as to supraspinal centers that modulate pain transmission in the spinal cord.

Inhibitory influences on receptive field size in the dorsal column nuclei.

Receptive fields (RFs) of neurons in the dorsal column nuclei (DCN) expand within minutes after the RFs are anesthetized via subcutaneous lidocaine injections (e.g., Pettit and Schwark). The mechanism of this rapid reorganization is of great interest. It has been proposed that such RF expansion results from a decline in inhibition within the DCN that unmasks previously ineffective synapses. To study the role of GABAergic inhibition in the DCN in controlling RF size, we applied by iontophoresis bicuculline methiodide to block gamma-aminobutyric acidA (GABA(A)) receptors and 2-OH-saclofen to block GABA(B) receptors. Blockade of GABA(A) receptors resulted in RF expansions in 79% of the neurons, while blockade of GABA(B) receptors resulted in RF expansions in 53% of the neurons. The effectiveness of receptor blockade in producing RF expansion was not related to neuronal response characteristics. Glutamate application resulted in RF expansions in only 2 of 23 neurons tested, suggesting that RF expansion was not simply due to increased excitability. The modality and adaptation characteristics of the expanded portions of the RFs were similar to those of the original RF. The results of the present study suggest that GABAergic inhibition can play a role in controlling RF size in the DCN, and that both GABA(A) and GABA(B) receptors may be involved in this process.

Stimulatory effect of substance P on sympathetic ganglia and spinal cord in culture.

Studies with organotypic culture of sympathetic ganglia and spinal cord revealed that substance P at concentrations of 10(-5) to 10(-12) M and 10(-5) to 10(-14) M exerts a marked growth-stimulating effect on sympathetic ganglia and spinal cord, respectively. In the presence of substance P, the intensity of sympathetic ganglion growth exceeds control values 3.0-4.8 times. The growth zone size of spinal cord explants increases under these conditions 2.0-5.2-fold. A feasible physiological significance of regulatory peptides in the growth and regeneration of nervous tissue as well as the role of noci-antinociceptive systems in histogenesis and regeneration are discussed.

Effects of opioid peptides and naloxone on nervous tissue in culture.

It was shown that opioid peptides stimulate nervous tissue growth in culture in the rat, which manifests itself in augmented outgrowth of neurites from explants and in an increase in the number of glial and fibroblast-like cells in the growth zone. The effects of opioid peptides ([Leu]- and [Met]-enkephalins, beta- and gamma-endorphins and some synthetic analogues of [Leu]-enkephalin) on the growth of organotypic cultures of rat sympathetic and dorsal root ganglia and spinal cord were investigated. Neurite outgrowth, cell composition, and size of the growth zone as well as the dynamics of its formation were estimated. Changes in the survival of neurons in dorsal root ganglion cultures were determined. The experiments were performed with living cultures as well as with fixed preparations. In experiments with sympathetic ganglia, it was demonstrated that a significant growth-promoting effect is exerted by peptides taken at concentrations of 10(-8) M to 10(-14) M. Naloxone does not eliminate the effects of peptides, but stimulates the growth at 10(-5) M to 10(-7) M. Studies with spinal cord revealed that naloxone (10(-6) M) enhances the response to [Leu]-enkephalin (10(-9) M). The survival of dorsal root ganglion neurons under the influence of a [leu]-enkephalin analog (10(-9) M) exceeds control values by approximately two to four times. Thus, opioid peptides were shown to exert a strong growth-promoting effect on nervous tissue in culture. This effect is dual: in neurons the peptides stimulate the outgrowth of neurites and their survival, while in glial cells they change the rate of their migration and, probably, their proliferation. It is suggested that opioid peptides, besides their already established functions, may play a role in the development and regeneration of nervous tissue.

A study of reception with the use of focused ultrasound. II. Effects on the animal receptor structures.

The possibility of stimulation of receptor structures with focused ultrasound (focused beam of high frequency mechanical waves) was investigated. Stimulation of single Pacinian corpuscle isolated from cat's mesentery resulted in receptor and action potentials. Stimulation of frog's ear labyrinth resulted in evoked potentials recorded from midbrain auditory area, their characteristics being much the same as those for responses to adequate sound stimuli. It is concluded that focused ultrasound is an advantageous agent for stimulation of various mechanoreceptors both isolated and, especially, located deep in the body. Some problems related to sensory specificity are discussed.

K and Na ion content in the Pacinian corpuscle fluid and its role in the activity of receptors.

1. Potassium and sodium concentrations within the Pacinian corpuscle fluid have been investigated in adult cats. The sodium and potassium contents of samples were estimated by means of integrative ultramicroflame photometry. 2. The analytical results showed the values of the potassium concentration in the Pacinian corpuscle fluid and in the blood plasma to be 6.19 +/- 0.72 and 2.78 +/- 0.38 mequiv/1, respectively. 3. The increasing excitability of the Pacinian corpuscle in potassium-rich solution was shown by electrophysiologic methods. In potassium-free solution two phases of changing receptor excitability were observed. 4. Removal of sodium from external solution reduced the receptor potential to 10% of its original value. 5. Some mechanisms of the increase in excitability of primary tissue mechanoreceptors and secondary mechanoreceptors of the sense organs are discussed.