Effect of neonatal capsaicin treatment on neural activity in the medullary dorsal horn of neonatal rats evoked by electrical stimulation to the trigeminal afferents: an optical, electrophysiological, and quantitative study.

To elucidate which glutamate receptors, NMDA or non-NMDA, have the main role in synaptic transmission via unmyelinated afferents in the trigeminal subnucleus caudalis (the medullary dorsal horn), and to examine the early functional effects of neonatal capsaicin treatment to the subnucleus caudalis, optical recording, field potential recording, and quantitative study using electron micrographs were employed. A medulla oblongata isolated from a rat 5--7 days old was sectioned horizontally 400-microm thick or parasagittally and stained with a voltage-sensitive dye, RH482 or RH795. Single-pulse stimulation with high intensity to the trigeminal afferents evoked optical responses mainly in the subnucleus caudalis. The optical signals were composed of two phases, a fast component followed by a long-lasting component. The spatiotemporal properties of the optical signals were well correlated to those of the field potentials recorded simultaneously. The fast component was eliminated by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 10 microM), while the long-lasting component was not. The latter increased in amplitude under a condition of low Mg(2+) but was significantly reduced by DL-2-amino-5-phosphonovaleric acid (AP5; 30 microM). Neonatal capsaicin treatment also reduced the long-lasting component markedly. In addition, the decreases in the ratio of unmyelinated axons to myelinated axons and in the ratio of unmyelinated axons to Schwann cell subunits of trigeminal nerve roots both showed significant differences (P<0.05, Student's t-test) between the control group and the neonatal capsaicin treatment group. This line of evidence indirectly suggests that synaptic transmission via unmyelinated afferents in the subnucleus caudalis is mediated substantially by NMDA glutamate receptors and documented that neonatal capsaicin treatment induced a functional alteration of the neural transmission in the subnucleus caudalis as well as a morphological alteration of primary afferents within several days after the treatment.

Fine structural organization of spinothalamic and trigeminothalamic lamina I terminations in the nucleus submedius of the cat.

We examined lamina I trigemino- and spinothalamic tract (TSTT) terminals labeled with Phaseolus vulgaris leucoagglutinin in the nucleus submedius (Sm), a nociceptive relay in the cat's thalamus. Volume-rendered (three-dimensional) reconstructions of ten lamina I TSTT terminals identified with light and electron microscopy were built from serial ultrathin sections by computer, which enabled the overall structures of the terminal complexes to be characterized in detail. Two fundamentally different terminations were observed: compact clusters of numerous boutons, which predominate in the dense focus of a lamina I terminal field in the Sm, and boutons-of-passage, which are present throughout the terminal field and predominate in its periphery. Reconstructions of cluster terminations reveal that all boutons of each cluster make synaptic contact with protrusions and branch points on a single dendrite and involve presynaptic dendrites (PSDs) in triadic arrangements, providing a basis for the secure relay of sensory information. In contrast, reconstructions show that boutons-of-passage are generally characterized by simple contacts with PSDs, indicating an ascending inhibitory lamina I influence. These different synaptic arrangements are consistent with physiological evidence indicating that the morphologically distinct nociceptive-specific and thermoreceptive-(cold)-specific lamina I TSTT neurons terminate differently within the Sm. Thus, a suitable structural substrate exists in the cat's Sm for the inhibitory effect of cold on nociception, a behavioral and physiological phenomenon of fundamental significance. We conclude that the Sm is more than a simple relay for nociception, and that it may be an integrative comparator of ascending modality-selective information that arrives from neurons in lamina I.

Quantitative electron-microscopic analyses of pulpal nerve fibres in the mouse lower incisor after neonatal capsaicin treatment.

A single dose of capsaicin (50 mg/kg) was injected subcutaneously into four mice on day 2 of life; four untreated mice were used as controls. Six months later, a drop of 30 microM capsaicin was instilled on to the cornea of all the mice and the number of times the eyes were wiped was counted to assess the effect of capsaicin on trigeminal sensory neurones. Ultrathin cross-sections were made of the apical pulp of the incisors on both sides of control (n = 8) and capsaicin-treated animals (n = 8). Electron micrographs of pulp nerves were taken and enlarged to a final magnification of x34,000. The numbers of unmyelinated axons in the pulps of all 16 incisors and of unmyelinated axons per Schwann cell in the pulps of four incisors each from the control and capsaicin-treated groups were counted. The short diameters of unmyelinated axons were measured with a computer-operated image analyser. The number of eye wipings was eight-fold less in the capsaicin-treated than in the normal group. This finding clearly indicated that capsaicin irreversibly affected the chemogenic nociceptive trigeminal neurones. The mean number of unmyelinated axons was 345 in controls and 217 (37.1% reduction) in capsaicin-treated animals. The number of unmyelinated axons of less than 0.6 microns dia was 41.5% less in capsaicin-treated mice than in controls. Thus, fine unmyelinated axons in the mouse incisor pulp are capsaicin sensitive, and they are assumed to be nociceptive fibres conveying pain stimuli from the tooth. Capsaicin affected Schwann cells, even those with few unmyelinated axons.(ABSTRACT TRUNCATED AT 250 WORDS)