Brain research
-
Subcutaneously (s.c.) administered [Arg8]vasopressin (AVP) potentiated seizures induced by intracerebroventricular (i.c.v.) injection of 1.95 mg pilocarpine (a muscarinic cholinergic agonist). A bell-shaped relation between dose and effect was found. I.c.v. pretreatment with a V1, V2 or oxytocin receptor antagonist was performed to determine whether and what type of receptor is involved in this proconvulsive effect of vasopressin. ⋯ Several selective antidiuretic agonists (V2), such as d[Val4]AVP, d[Phe2,Val4,D-Arg8]vasopressin (3 microg), [Val4,D-Arg8]vasopressin (3 microg) and d[Val4,D-Arg8]vasopressin (3 microg) were active. Other selective antidiuretic compounds, such as [Val4]AVP, dAVP, d[Tyr(Me)2]AVP and HO[D-Arg8]vasopressin (3 microg) did not influence seizures. These results demonstrate that a combination of substitution of aminoacid 4 (Gln) by Val and to a lesser extent deamination and the D-arginine form yield an active molecule, which can potentiate pilocarpine induced seizures and suggest the existence of a V2 receptor subtype in the brain.
-
Nerve injury leads to central neuroimmunologic responses that may be integral to the development and maintenance of chronic neuropathic pain in humans. Recent data have demonstrated that cytokines and growth factors may be strongly implicated in the generation of pain states at both peripheral and central nervous system sites. We utilized immunohistochemical methods to investigate this phenomenon in rat models of neuropathic pain. ⋯ This study demonstrated increased specific cytokine and growth factor-like expression in the spinal cord following peripheral nerve injuries. It also showed a differential expression of bFGF in two distinct mononeuropathy models. These results provide further evidence that central cytokine production via a neuroimmune cascade may be involved in the development and maintenance of behaviors that mimic neuropathic pain following nerve injury.
-
We used near-infrared spectroscopy (NIRS) to study non-invasively changes in cerebral hemoglobin oxygenation in the frontal and parietal cortex during performance of a verbal fluency task in patients with Alzheimer's disease (AD). Whereas healthy elderly subjects (n = 19, age 67 +/- 10 years) showed increases in concentrations of oxygenated hemoglobin [HbO2] (mean (arbitrary units) +/- S. E. ⋯ Simultaneous NIRS-[HbT] and PET-rCBF measurements showed a significant correlation both when calculated in a 'banana' shaped volume approximated by using cortical thresholds as well as when calculated in a semisphere volume of brain tissue beneath the optodes placed on the head surface (patients with AD, n = 10). The correlation was dependent on the assumed penetration depth of the near-infrared light and was best for all three NIRS variables ([HbO2], [HbR] and [HbT]) when calculated using a semisphere radius of 0.45 cm to 1.35 cm. In conclusion, in Alzheimer's disease a marked reduction of regional cerebral blood flow and cerebral hemoglobin oxygenation may occur during activation of brain function, probably mainly in degenerating brain areas, such as the parietal cortex.
-
Recently, local injection of morphine in the dorsal raphe nucleus (DRN) has been shown to increase serotonin release in the forebrain of unanesthetized rats. This study investigated the site of action of opioids in rat brain slices containing the DRN. Postsynaptic currents (PSCs), measured intracellularly under voltage clamp, were induced in serotonergic neurons with bath and microiontophoretic applications of NMDA to activate local neurons. ⋯ Consistent with the reduction in PSCs, ENK inhibited/hyperpolarized the great majority (81%) of non-serotonergic neurons recorded extra- and intracellularly in the DRN; the ENK effect reversed polarity at -99 +/- 9 mV, close to the potassium reversal potential. In contrast, ENK inhibited/hyperpolarized only 28% of serotonergic neurons; in the affected cells, the ENK effect, blocked by CTOP, had its reversal potential shifted with change of extracellular potassium in agreement with the value predicted by the Nernst equation for a potassium conductance; serotonin occluded the ENK inhibition. Taken together, these results indicate that opioids inhibit both local GABAergic and glutamatergic cells projecting onto DRN serotonergic neurons.
-
Intraplantar injection of dilute formalin evokes brief (Phase 1) and persistent (Phase 2) increases in primary afferent activity, pain behavior, and cardiovascular responses, and induces spinal cord Fos-like immunoreactivity (Fos-LI). Although previous studies demonstrated that the destruction of small diameter primary afferents with neonatal capsaicin treatment decrease formalin-evoked nociception, these studies only evaluated behavioral responses, and did not distinguish between Phase 1 and 2. To address these questions, we simultaneously evaluated formalin-evoked pain behavior (flinching of the afflicted paw), cardiovascular responses (heart rate and mean arterial pressure), and lumbar spinal cord Fos expression in control rats and in rats treated with capsaicin (100 mg/kg) one day postpartum. ⋯ Also, in capsaicin-treated rats, we counted 59% fewer Fos-labeled neurons in the spinal cord. These results indicate that capsaicin-sensitive afferents contribute to formalin-evoked behavioral and cardiovascular responses and to spinal cord neuronal responses. The differential effect of neonatal capsaicin on nociception during Phase 1 and Phase 2 suggests that sensitization mechanisms during Phase 1 do not contribute to the magnitude of nociceptive responses during Phase 2.