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Systemic clonidine activates neurons of the dorsal horn, but not the locus ceruleus (A6) or the A7 area, after a formalin test: the importance of the dorsal horn in the antinociceptive effects of clonidine.

PURPOSE: In order to clarify the principal site for the antinociceptive effects of clonidine, we investigated the nociceptive behavior and neural activity (c-fos staining) of the dorsal horn (DH), locus ceruleus (LC), and A7 area after a formalin test in normal saline- or clonidine-injected rats. METHODS: Thirty-six rats were divided into 6 groups as follows: formalin test + saline (FS); formalin test + clonidine (1 mg.kg(-1)) (FC1); formalin test + clonidine (10 mg.kg(-1)) (FC10); saline (S); clonidine (1 mg.kg(-1)) (C1); and clonidine (10 mg.kg(-1)) (C10). Normal saline or clonidine was injected intraperitoneally 30 min before the formalin test. In the FS, FC1, and FC10 groups, 10% formalin was injected into the left rear paw. All rats were killed 2.5 h after normal saline or clonidine injection. Sections of the lumbar spinal cord, LC, and A7 area were processed for c-fos immunohistochemistry using the avidin-biotin peroxidase complex method. To evaluate the sedative effects of clonidine, we investigated the loss of righting reflex (LORR) for 90 min in 6 other rats as follows: clonidine (1 mg.kg(-1)) (n = 3) and clonidine (10 mg.kg(-1)) (n = 3). RESULTS: The FC10 group showed fewer nociceptive behaviors and higher c-fos expression in the DH, but not in the A7 area, as well as lower c-fos expression in the LC than rats in the FS and FC1 groups (P < 0.05). The C10 group showed lower c-fos expression in the LC than that of rats in the S and C1 groups (P < 0.05). No rats exhibited LORR. CONCLUSION: The antinociceptive effects of clonidine might be mediated primarily by neural activity in the DH.

Adrenergic alpha-Agonists↗

Structure-function relationships in rat medullary and cervical dorsal horns. II. Medullary dorsal horn cells.

In Nembutal-anesthetized rats, 31 physiologically identified medullary dorsal horn (MDH) cells were labeled with horseradish peroxidase (HRP). Ten responded only to deflection of one or more vibrissae. Six cells were activated by guard hair movement only, six by deflection of guard hairs or vibrissa(e), and seven by pinch of facial skin with serrated forceps. Different classes of low-threshold cells could not be distinguished on the basis of their somadendritic morphologies or laminar distribution. Neurons activated by multiple vibrissae were unique, however, in that one sent its axon into the medial lemniscus, and three projected into the trigeminal spinal tract. None of the guard hair-only or vibrissae-plus-guard hair neurons had such projections. Cells that responded best to noxious stimulation were located mainly in laminae I, II, and deep V, while neurons activated by vibrissa(e) and/or guard hair deflection were located in layers III, IV, and superficial V. Low-threshold neurons generally had fairly thick dendrites with few spines, whereas high-threshold cells tended to have thinner dendrites with numerous spines. Moreover, the dendritic arbors of low-threshold cells were, for the most part, denser than those of the noxious cells. Neurons with mandibular receptive fields were located in the dorsomedial portion of the MDH; cells with ophthalmic fields were found in the ventrolateral MDH, and maxillary cells were interposed. Cells sensitive to deflection of dorsal mystacial vibrissae and/or guard hairs were located ventral to those activated by more ventral hairs. Neurons with rostral receptive fields were found in the rostral MDH, while cells activated by hairs of the caudal mystacial pad, periauricular, and periorbital regions were located in the caudal MDH. Receptive-field types were encountered that have not been reported for trigeminal primary afferent neurons: multiple vibrissae; vibrissae plus guard hairs; and wide dynamic range. The latter two can be explained by the convergence of different primary afferent types onto individual neurons. Our failure to find a significant relationship between dendritic area (in the transverse plane) and the number of vibrissae suggests that primary afferent convergence may not be responsible for the synthesis of the multiple vibrissae receptive field. Excitatory connections between MDH neurons may, therefore, account for multiple vibrissae receptive fields in the MDH.

Animals↗

Cortical projections to superficial laminae of the dorsal horn and to the ventral horn of the spinal cord in the North American opossum. Studies using the orthograde transport of WGA-HRP.

The orthograde transport of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) has been used to study the distribution of corticospinal axons in adult and pouch-young opossums. As predicted from the results of degeneration and autoradiographic experiments, injections of WGA-HRP into limb areas of somatic motor-sensory cortex labeled axons in the dorsal and lateral funiculi of the cervical and upper thoracic spinal cord which could be traced to dense terminal zones in laminae III-VI. In addition, we obtained evidence for the presence of a few cortical axons in the ventral white matter and for innervation of the medial part of laminae I and II, laminae VII and VIII and lamina X. A few cortical axons are even present in lamina IX.

Animals↗