Brain research
-
The possible control by opioids of the spinal release of calcitonin gene-related peptide-like material (CGRPLM) was investigated in halothane-anaesthetized rats whose intrathecal space was perfused with an artificial cerebrospinal fluid. Morphine (20 mg/kg i.v.; or at 10-100 microM added to the perfusing fluid), the mu selective agonist DAGO (10 microM) and the kappa selective agonist U 50488 H (10 microM) did not affect the spontaneous outflow of the CGRPLM. In contrast, the selective delta agonist DTLET (10 microM) significantly increased CGRPLM release. ⋯ Indeed, a significant decrease in the spinal release of CGRPLM release could be evoked by the combined addition of U 50488 H (10 microM) plus DAGO (10 microM) to the perfusing medium, indicating that the simultaneous stimulation of both kappa and mu receptors is required for this negative control to occur. This could notably be achieved with morphine (10 microM) in the presence of naltrindole (10 microM) which also produced a significant reduction in the spinal release of CGRPLM. In conclusion, morphine per se did not change CGRPLM release because this drug triggers opposite positive (through the stimulation of delta receptors) and negative (through the concomitant stimulation of both kappa and mu receptors) control mechanisms within the rat spinal cord.
-
In an attempt to define areas of the brain that respond to stressors and influence immune function, we have previously identified stress-induced, c-Fos-immunoreactive areas of the diencephalon. We found that c-Fos was strongly expressed in cells of the paraventricular nuclei (some of which contain corticotropin-releasing hormone (CRH)) and other hypothalamic areas directly associated with autonomic function. To further characterize the presumptive pathways mediating stress-induced immune alterations, including the assessment of brainstem catecholaminergic neuron involvement, the induction of c-Fos immunoreactivity was examined in the brainstem of rats exposed to conditioned and unconditioned, immunomodulating stimuli. ⋯ Conditioned animals re-exposed to the conditioned stimulus showed c-Fos induction in these same areas but to a lesser degree. Control animals exposed only to the conditioning stimulus (CS) (electronic tone) in the absence of the US, expressed very little, if any, c-Fos activity in the above loci except for a small degree of baseline expression in the PAG. These results further confirm the role of autonomic and endocrine pathways as mediators of the stress response and will help to more fully characterize the pathways of stress-induced immune alteration.
-
An animal model of peripheral neuropathy resulting in a unilateral hyperalgesia has recently been developed. The N-methyl-D-aspartate (NMDA) antagonist MK-801 reduces the thermal hyperalgesia observed in this model. The goal of the present study was to determine whether the immunohistochemical changes in dorsal horn peptides shown by neuropathic animals could also be modified by MK-801. ⋯ However, this global increase failed to mask the changes in staining density in neuropathic animals following MK-801 treatment. The results suggest a functional interaction between excitatory amino acids (EAAs) and SP, with activation of NMDA receptors mediating depletion of SP in neuropathic animals. It is suggested that SP-containing interneurons are a target of the EAAs in the dorsal horn.
-
The effect of morphine was examined under identical conditions on (a) antidromic vasodilatation, an 'efferent' function of C-nociceptors in the skin, and (b) afferent responses to heat and pressure of C-polymodal nociceptors. Morphine caused a large, naloxone-reversible, fall in peak antidromic vasodilatation (ADV). However it caused no significant change in heat or mechanical excitability of C-polymodal nociceptors in normal or mildly inflamed skin. The mechanisms by which morphine might affect efferent, but not afferent, functions of C-nociceptors are discussed.