Brain research
-
Comparative Study
Differential induction of c-fos expression in brain nuclei by noxious and non-noxious colonic distension: role of afferent C-fibers and 5-HT3 receptors.
Experimental animal models have been established to gain insight into the pathogenesis and the mechanisms of visceral hyperalgesia in the irritable bowel syndrome (IBS). However, data about the mechanisms and pathways involved in the induction of neuronal activity in forebrain and midbrain structures by a physiological GI stimulus, like colonic distension (CD), in the range from non-noxious to noxious intensities are scarce. Thus, the effect of proximal CD with non-noxious (10 mmHg) and noxious (40 and 70 mmHg) stimulus intensities on neuronal activity in brain nuclei, as assessed by c-fos expression, was established. ⋯ Activation of NTS neurons at such a condition seems to be partially mediated via capsaicin-sensitive vagal afferents and 5-HT(3) receptors. In contrast, activation of brain nuclei in the di- and telencephalon by nociceptive mechanical stimulation of the proximal colon, as assessed by c-fos expression, is partially mediated by capsaicin-sensitive, non-vagal afferents, and independent of neurotransmission via 5-HT(3) receptors. The modulation of CD-induced c-fos expression exclusively in the NTS by granisetron points to a role of 5-HT(3) receptor antagonists in the modulation of vago-vagal sensomotoric reflexes rather than an influence on forebrain nuclei involved in nociception.
-
Vascular dysfunction is important in the pathogenesis of peripheral complications of diabetes. However, the effects of diabetes on cerebral blood flow and the role of vascular deficits in the pathogenesis of diabetic encephalopathy are still unknown. The present study examined whether experimental diabetes is associated with reduced cerebral blood flow and whether treatment with enalapril can improve cerebral perfusion and function (blood flow and functional cerebral deficits). ⋯ Cerebral perfusion is reduced in diabetic rats compared to controls. Treatment aimed at the vasculature can improve cerebral blood flow, deficits in Morris maze performance and long term potentiation. These findings suggest that vasculopathy plays a role in the development of cerebral dysfunction in diabetic rats.
-
Lactoferrin (LF) is a multifunctional protein that is found in milk, neutrophils, and other biological fluids. Although LF and the LF receptor have been identified in the central nervous system (CNS), the physiological role of LF remains unknown. We found that bovine milk-derived LF (BLF) reduces nociception in various pain models, as shown by the formalin test, hot plate test, and acetic acid writhing test in rats. ⋯ The antinociceptive effects of BLF were blocked by naloxone treatment, even though prostaglandin E(2) (PGE(2)) production in the ascites fluid that accumulated during the writhing test was not affected by BLF. Intrathecal (i.t.) application of BLF caused marked antinociceptive effects that were reversed by co-administration of a specific mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-NH(2) (CTOP), or by naloxone during the formalin test. We conclude that LF possesses mu-opioid receptor-mediated antinociceptive activity in the spinal cord.
-
Spinally administered muscarinic receptor agonists or acetylcholinesterase inhibitors can produce antinociception. However, the mechanisms of the action of cholinergic agents in the spinal cord are not fully understood. Activation of spinal muscarinic receptors evokes gamma-aminobutyric acid (GABA) release, which reduces the glutamatergic synaptic input to dorsal horn neurons through GABA(B) receptors. ⋯ Furthermore, the antiallodynic effect of intrathecal neostigmine and muscarine was largely eliminated by CGP55845 in diabetic rats. These data suggest that the GABA(B) receptors in the spinal cord mediate both the antinociceptive and antiallodynic actions of intrathecal muscarine or neostigmine in normal rats and in a rat model of diabetic neuropathic pain. This study provides new functional evidence that activation of spinal GABA(B) receptors is one of the important mechanisms underlying the antinociceptive action of intrathecal cholinergic agents.
-
Serotonin type 2 (5-HT(2)) receptors reportedly inhibit neuropathic pain in the spinal cord, but little is known about how spinal 5-HT(2) receptors might act against such abnormal sensitivity. We examined whether the cholinergic and tachykinin systems were involved in the antiallodynic effect of intrathecally administered 5-HT(2) receptor agonists in rats with nerve injury. Allodynia was produced by tight ligation of the left L5 and L6 spinal nerves, and determined by applying von Frey hairs to the left hindpaw. ⋯ Antiallodynic effects of 5-HT(2) receptor agonists were attenuated by the 5-HT(2A) receptor antagonist ketanserin (30 micro g), but not by the 5-HT(2C) receptor antagonist RS-102221 (40 micro g). Muscarinic receptor antagonists (30 micro g each), the choline uptake blocker (10 micro g), and the NK(1) receptor antagonist (30 micro g) also inhibited the antiallodynic effects of 5-HT(2) receptor agonists. Antiallodynic effects of intrathecally administered 5-HT(2) receptor agonists may be mediated by spinal release of acetylcholine induced via 5-HT(2A) and NK(1) receptors.