Characteristics of propriospinal modulation of nociceptive lumbar spinal dorsal horn neurons in the cat.

The segmental and laminar origin of propriospinal antinociceptive systems in the cat spinal cord and the modes to activate them are characterized. The experiments were performed on pentobarbital-anesthetized cats with a high cervical spinalization. Recordings were made from single lumbar spinal dorsal horn neurons responding to noxious radiant skin heating and to innocuous mechanical skin stimuli. The segmental and laminar origin of heterosegmental, propriospinal neurons modulating background activity and nociceptive responses were identified and the conditions to activate them were characterized. Conditioning noxious front paw stimulation and superfusion of the cervical enlargement with L-glutamate, but not with substance P, reduced noxious heat-evoked responses of about 50% of all lumbar neurons tested. Glutamate superfusions of the lower thoracic or upper sacral spinal cord enhanced background activity and reduced nociceptive responses of most lumbar spinal dorsal horn neurons. Superfusions with substance P or somatostatin were ineffective. Glutamate microinjections into the superficial layers of the thoracic, upper lumbar or sacral dorsal horn ipsi- or contralateral to the recording sites or into lamina VIII of the ipsilateral thoracic or upper lumbar cord reduced noxious heat-evoked responses with or without changes in the level of background activity. It is concluded that propriospinal neurons originating from circumscribed areas of the cervical, thoracic, lumbar or sacral spinal cord independently modulate background activity and noxious heat-evoked responses of multireceptive lumbar spinal dorsal horn neurons. The incidence and efficacy of propriospinal antinociceptive stimulation sites was found to be as high as for the classical region of endogenous antinociception, the midbrain periaqueductal gray.

Suppression of a hind limb flexion withdrawal reflex by microinjection of glutamate or morphine into the periaqueductal gray in the rat.

Microinjection into the midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF) of the neuronal excitant glutamate produces analgesia, and suppresses the responses of a fraction of spinal dorsal horn neurons to noxious heat applied to ventral hind paw skin. Microinjection of morphine into the PAG also produces analgesia, but has been reported to frequently facilitate, as well as to suppress or have no effect, on nociceptive spinal neurons. In anesthetized rats, we tested whether (a) glutamate microinjections into PAG or LRF, and (b) morphine microinjections into PAG, affected the isometric force of hind limb withdrawal elicited by the same noxious heat stimuli on the hind paw as used in single-unit studies of dorsal horn neurons. Glutamate (0.5 M; 0.1-0.5 microliter) microinjected at 9/12 PAG and 8/10 LRF sites suppressed the reflex, and had no effect or facilitated the reflex from the remaining sites. Morphine (5 micrograms in 0.5 microliter) microinjected at each of 10 PAG sites suppressed the reflex in a naloxone-reversible manner. Suppression usually began shortly after morphine, peaked at 20-40 min, and lasted greater than 60 min. The integrated flexion reflex thus appears to be more susceptible to chemical midbrain stimulation under these experimental conditions, compared to previous studies of single dorsal horn neurons.

Microinjections of glutamate or morphine at coincident midbrain sites have different effects on nociceptive dorsal horn neurons in the rat.

Responses of single lumbar spinal neurons to noxious skin heating (50 degrees C, 10 s) were electrophysiologically recorded in barbiturate-anesthetized rats. Responses of all neurons were suppressed by electrical stimulation in the midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF). Microinjection of glutamate (GLU, 0.1-0.3 microliter, 0.5 M) into the PAG rapidly (within 15 s) suppressed (to 13-55% of control) the responses of 6/16 neurons with recovery within 8 min. The remainder were affected less at even higher doses (0.5-1 microliter). Responses of 4/10 neurons were suppressed following GLU microinjected into the LRF. We also tested effects of microinjection of morphine (MOR, 5 micrograms/0.5 microliter) into GLU-sensitive and insensitive PAG sites. Responses of 4 neurons were unaffected, 4 were enhanced (to 130-155%), and 2 suppressed (to 43 and 57%) following MOR in PAG, with enhancement or suppression beginning within 12-20 min and lasting 40 to over 70 min. The differing effects of GLU and MOR may reflect different mechanisms for the descending modulation of spinal nociceptive transmission.

B vitamins suppress spinal dorsal horn nociceptive neurons in the cat.

To explore the role of vitamin B in neural mechanisms of analgesia, we investigated the effect of a compound of vitamins B1, B6 and B12 (Neurobion, E. Merck) on the nociceptive responses of single neurons in the spinal cord dorsal horn in anesthetized cats. Intrathecal superfusion of Neurobion, using a small pool placed on the spinal surface, produced a significant dose-dependent depression in the responses evoked by noxious skin heating (50 or 52 degrees C, 10 s) of hindfoot skin, but not of spontaneous activity in dorsal horn neurons. These results indicate that the therapeutic effect of vitamin B compounds in the clinical management of pain may involve a suppression of nociceptive transmission at the spinal level.