Prenatal exposure to methamphetamine (METH) increases nociceptive sensitivity in adult rats. As the strong analgesics have high abuse potential and drugs of abuse are known to have analgesic properties, the aim was to study analgesic effect of different psychostimulants in control and prenatally METHexposed rats. Latencies of withdrawal reflexes of hind limbs and the tail on thermal nociceptive stimuli were repeatedly measured in 15-min intervals after the application of 5 mg/kg s.c. of amphetamine (AMPH), methamphetamine (METH), cocaine (COC), 3,4-methylenedioxymethamphetamine (MDMA) or morphine (MOR). In all groups, AMPH induced on hind limbs stronger analgesia than METH and MDMA whereas COC and MOR were practically without any effect. On the tail, effect of AMPH did not differ from that of MOR. All psychostimulants increased defecation in comparison with MOR and in all groups the number of defecation boluses positively correlated with analgesia of the hind limbs. We did not confirm that prenatal exposure to METH makes adult rats more sensitive either to same drug or to other psychostimulants. The different analgesic potencies of psychostimulants and MOR at different body sites indicate the possible existence of a somatotopic organization of pain inhibition, which is controlled by different mechanisms., A. Yamamotová, R. Šlamberová., and Obsahuje seznam literatury
Galanin and galanin receptors (GalRs) have been reported to be
involved in the transmission and modulation of nociceptive
information in the central nervous system (CNS). However, the
underlying mechanism of the antinociception of GalRs in
neuropathic pain remains unclear. This study investigated the
antinociception induced by galanin receptor 1 (GalR1) via protein
kinase A (PKA) signaling pathway in the nucleus accumbens
(NAc) of rats with neuropathic pain. A mononeuropathy model
was replicated by ligation of the left sciatic nerve, following which
the expression of phospho-PKA (p-PKA) in the NAc were
markedly up-regulated at 14th and 28th day after ligation of sciatic
nerve, and p-PKA expression was down-regulated by intra-NAc
injection of GalR1 agonist M617, but the GalR1 antagonist M35
did not have an effect. We also found that M35 in the NAc
blocked the M617-induced increase in the hind paw withdrawal
latencies (HWLs) of rats with mononeuropathy, but M35 alone
had no effect on HWLs, and PKA inhibitor H-89 attenuated the
M617-induced an increase in the HWLs. These results suggested
that GalR1 induced an antinociception via inhibiting PKA
activation, implying that GalR agonists may be potential and
potent therapeutic options to treat chronic neuropathic pain.
Galanin (GAL) is suggested to be a neuropeptide involved in pain transmission. In this study we tried to determine, whether the increase of GAL concentration in brain cells affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles. The experiments were carried out on rats under chloralose anesthesia. The study objectives were realized using the method allowing to record the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation during the perfusion of the cerebral ventricles with solutions containing tested compounds. Perfusion of the cerebral ventricles with GAL concentration-dependently inhibited the ETJ amplitude. The antinociceptive effect of GAL was blocked by a galanin receptor antagonist, galantide (GLT) and by opioid antagonists: non-selective naloxone (Nal) and μ-selective β-funaltrexamine (β-FNA). In contrast, a δ-opioid receptor antagonist, naltrindole (NTI) or the κ-opioid receptor antagonist, nor-binaltrophimine (nor-BNI) did not inhibit the effect of GAL. The antinociceptive effect of GAL was more pronounced when GAL was perfused in combination with other neuropeptides/neurohormones, such as endomorphin-2 (EM-2), vasopressin (AVP) and oxytocin (OT). The present results demonstrate that in the orofacial area analgesic activity is modulated by GAL, OT and AVP and that EM-2-induced antinociception involves GAL., M. Zubrzycka, A. Janecka., and Obsahuje bibliografii a bibliografické odkazy