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PubMedDate not supplied

Neural changes in acute arthritis in monkeys. I. Parallel enhancement of responses of spinothalamic tract neurons to mechanical stimulation and excitatory amino acids.

Somatosensory neurons of the spinal cord, including projection neurons, become hyperexcitable to mechanical stimuli during the development of experimental arthritis in rats and cats and hence are suggested to participate in the generation of arthritic hyperalgesia in humans. The experiments described here show a potentiation of the responses of spinothalamic tract (STT) neurons in monkeys during the development of an acute arthritis. The results demonstrate that the responses of STT neurons to mechanical stimuli and to iontophoretically applied excitatory amino acids (EAAs), particularly those acting at non-N-methyl-D-aspartate (non-NMDA) receptors, become enhanced during the development of inflammation produced by intra-articular injection of kaolin and carrageenan. Since the enhancement of both responses follows a similar time course, the results of this work suggest a role for EAAs in the hyperalgesia associated with arthritis and hence may provide a possible pharmacologic target for alleviation and/or prevention of arthritic pain.

Acute Disease↗
PubMed1991

Two forms of inhibition of spinothalamic tract neurons produced by stimulation of the periaqueductal gray and the cerebral cortex.

1. Recordings were made from the lumbosacral spinal cord in anesthetized macaque monkeys. The inhibitory effects of electrical stimulation of the periaqueductal gray (PAG) and the cerebral cortex or cerebral peduncle (CP) were tested and compared by recording 1) cord dorsum potentials evoked by stimulation of the sural nerve, 2) discharges recorded extracellularly, and 3) membrane potentials recorded intracellularly from spinothalamic tract (STT) neurons at rest (background activity) or in response to stimulation of the sural nerve. 2. Stimulation of the cortex or in the CP preferentially reduced the amplitude of the N1 and N2 waves of the cord dorsum potential evoked by stimulation of the sural nerve, without affecting the N3 wave. Stimulation of the PAG, on the other hand, reduced the amplitude of the N3 wave with little effect on the N1 and N2 waves. 3. The activity of 62 STT neurons was recorded extracellularly. Stimulation of the PAG or the cortex/CP inhibited nonpreferentially the responses of the neurons in the superficial laminae to all afferent inputs. On the other hand, stimulation of the PAG or the cortex/CP inhibited preferentially the responses of most STT neurons in deep layers of the dorsal horn to the small or large afferent input, respectively. 4. Thirty-five neurons were recorded intracellularly. The membrane potential of the neurons averaged -45.5 +/- 10.1 (SD) mV. All neurons were recorded in laminae III-VI; the neurons were of the wide-dynamic-range (WDR) type and had background activity. 5. The inhibitory effects of stimulation of the PAG were tested on all 35 neurons. In 32 of the neurons, stimulation of the PAG evoked a hyperpolarization. The background activity of the neurons was reduced (generally it completely ceased) by the hyperpolarization. In three neurons stimulation of the PAG did not evoke a hyperpolarization and the background activity of the neurons did not change. Nevertheless, the responses of these three neurons to afferent input were inhibited by stimulation in the PAG. 6. The inhibitory effects of stimulating the cortex and/or the CP were tested in 26 of the 35 neurons. Stimulation of the cortex and/or the CP evoked a hyperpolarization in all the neurons, although, in 10 of the 26 neurons, stimulation of the CP also evoked a depolarization. The hyperpolarization generally blocked the background activity of the neurons. 7. The effective stimuli in the PAG and the cortex/CP to evoke a hyperpolarization in STT neurons were short, high-frequency trains of pulses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

Memantine attenuates responses of spinothalamic tract cells to cutaneous stimulation in neuropathic monkeys.

Several lines of evidence indicate that N-methyl-D-aspartate (NMDA) receptors play an important role in nociception in general and in pathological pain in particular. It has been previously demonstrated in behavioral studies that NMDA receptor antagonists attenuate pathological pain in humans and nociceptive behaviors in animals. In the present study, we investigated the effect of the NMDA receptor antagonist memantine (MEM) on the responses of spinothalamic tract (STT) cells in normal and neuropathic monkeys. Memantine was delivered into the spinal cord through a microdialysis fiber acutely implanted into the dorsal horn. Responses of STT cells to peripheral stimulation within their receptive fields were recorded before and after MEM infusion. In normal animals (n = 7), 10 mm MEM did not affect STT cell (n = 7) baseline activity or responses to mechanical stimuli (brush, press or pinch). In neuropathic animals (n = 6), 1.0, 3.0, 10.0 and 100 mm MEM did not affect baseline activity of STT cells (n = 7); however, in a dose-dependent fashion, it significantly reduced responses of these cells to all cutaneous stimuli. The data suggest that MEM can have a direct effect on STT cells, blocking NMDA receptors known to be present on this cell population and, furthermore, may be a therapeutic agent for chronic pain.

Journal Article↗
PubMed1992

Segmental organization of visceral and somatic input onto C3-T6 spinothalamic tract cells of the monkey.

1. Referred pain of visceral origin has three major characteristics: visceral pain is referred to somatic areas that are innervated from the same spinal segments as the diseased organ; visceral pain is referred to proximal body regions and not to distal body areas; and visceral pain is felt as deep pain and not as cutaneous pain. The neurophysiological basis for these phenomena is poorly understood. The purpose of this study was to examine the organization of viscerosomatic response characteristics of spinothalamic tract (STT) neurons in the rostral spinal cord. Interactions were determined among the following: 1) segmental location, 2) effects of input by cardiopulmonary sympathetic, greater splanchnic, lumbar sympathetic, and urinary bladder afferent fibers, 3) location of excitatory somatic field, e.g., hand, forearm, proximal arm, or chest, 4) magnitude of response to hair, skin, and deep mechanoreceptor afferent input, and 5) regional specificity of thalamic projection sites. 2. A total of 89 STT neurons in segments C3-T6 were characterized for responses to visceral and somatic stimuli. Neurons were activated antidromically from the contralateral ventroposterolateral oralis or caudalis nuclei of the thalamus. Cell responses to visceral and somatic stimuli were not different on the basis of the thalamic site of antidromic activation. Recording sites for 61 neurons were located histologically; 87% of lesion sites were located in laminae IV-VII or X. There was no relationship between response properties of the neurons and spinal laminar location. 3. Different responses to visceral stimuli were observed in three zones of the rostral spinal cord: C3-C6, C7-C8, and T1-T6. In C3-C6, urinary bladder distension (UBD) and electrical stimulation of greater splanchnic and lumbar sympathetic afferent fibers inhibited STT cells. Electrical stimulation of cardiopulmonary sympathetic afferents increased cell activity in C5 and C6 and either excited or inhibited STT cells in C3 and C4. In the cervical enlargement (C7-C8), STT cells generally were either inhibited or showed little response to stimulation of visceral afferent fibers. In T1-T6, input from greater splanchnic and cardiopulmonary sympathetic afferent nerves increased activity of STT cells. Lumbar sympathetic afferent input inhibited cells in T1-T2 and had little effect on cells in T3-T6, whereas UBD decreased cell activity in all segments studied. 4. In general, stimulation of somatic structures increased activity of STT neurons in segments that received primary afferent innervation from the excitatory somatic receptive field or in the segments immediately adjacent to these segments. Only input from the forelimb, especially the hand, markedly excited cells in C7 and C8.+

Afferent Pathways↗
PubMed1984

Collateralization in the spinothalamic tract: new methodology to support or deny phylogenetic theories.

Components of the spinothalamic system that ascend in the anterolateral funiculus are reviewed. The presence of collateralization in this system in mammals is discussed with regard to theories of the phylogenetic development of pathways. The major theory investigated suggested that collateralization is an intermediate stage between a multisynaptic pathway and a direct non-collateralized lemniscus. The evidence and theories are reviewed. Methods for confirming or rejecting this theory are discussed. The literature reporting ascending spinal projections for non-mammalian vertebrates is reviewed. Certain reptiles have projections analogous to both the mammalian neospinothalamic and paleospinothalamic tracts. The presence of spinothalamic projections in elasmobranchs and amphibians is still controversial. Confirmation of earlier reports of projections in salamander and dogfish shark based on degeneration techniques have not been done. In addition, results from too few species of these classes have been reported. However, it is possible that paleospinothalamic connections are present in some species (e.g. salamander, nurse shark) and not in others (e.g. frog, dogfish shark) of the same class. Spinothalamic projections have not been reported for teleosts. A plea for new research in this area is made.

Animals↗
PubMed1998

Phrenic nerve inputs to upper cervical (C1-C3) spinothalamic tract neurons in monkeys.

Afferent input from the phrenic nerve enters mid-cervical spinal segments, and previous results in monkeys show that mid-cervical spinothalamic (STT) neurons are activated by groups II and III phrenic afferent input arising from the diaphragm. In rats, dorsal horn neurons in C1-C2 segments receive phrenic input stimulated above the heart, but are not activated by phrenic input arising from diaphragm or abdomen. It is not known if this differential organization occurs in primate STT neurons. We hypothesized that high cervical STT neurons in monkeys also would be preferentially activated by phrenic inputs from thoracic structures, such as the pericardium. We examined extracellular discharge rate of C1-C3 STT neurons for responses to electrical stimulation of phrenic nerve fibers. Responses to stimulation of ipsilateral phrenic fibers above the heart were compared to effects of input stimulated below the heart and also to effects of contralateral phrenic input. We concluded that upper cervical STT neurons are most strongly excited by ipsilateral input from small diameter phrenic fibers arising from thoracic structures, but that group III and IV input from diaphragmatic fibers as well as input from contralateral phrenic fibers have a lesser effect on C1-C3 STT neurons and thus might be involved in nociceptive processing.

Afferent Pathways↗