Biomedical subjects

T Lundeberg

Publications and source records attributed to T Lundeberg.

At least 19 recordsLinked to original sources

PubMed2001

Anti-nociceptive effect of neuropeptide Y in periaqueductal grey in rats with inflammation.

Experimental inflammation was induced by subcutaneous injection of carrageenan into the left hindpaw of rats. Intra-periaqueductal grey (PAG) injection of 0.02 or 0.1 nmol of neuropeptide Y (NPY), but not 0.004 nmol, induced significant increases in hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats with inflammation. Furthermore, the anti-nociceptive effect of NPY was blocked partly by following intra-PAG injection of the Y1 receptor antagonist NPY28-36. The results demonstrated that NPY plays an anti-nociceptive role in PAG in rats with inflammation, in which Y1 receptor is involved.

Animals↗

PubMed2000

RT-PCR ELISA method for the analysis of neurotrophin mRNA expression in brain and peripheral tissues.

The levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in brain and periphery are susceptible to changes during development and as result of different physiopathological conditions, such as stress and aging and during the onset and progression of neurological and autoimmune diseases. Despite the sensitive methods for measurement of neurotrophin protein levels in different tissues, no easily applicable methods to evaluate changes in the level of NGF and BDNF mRNA expression within physiological range have been described. This study reports the development of a reproducible and simple procedure for measurement of neurotrophin mRNA expression in brain and peripheral tissues based upon an enzyme linked immunosorbent assay (ELISA) detection system of reverse transcriptase-polymerase chain reaction (RT-PCR) products. The major advantages of this RT-PCR ELISA procedure is to allow the co-amplification of diverse mRNAs starting from small amounts of tissues; to contemporaneously test a large number of samples; to be rapid and to use only commercial reagents and widely available equipment. The procedure could also be useful in studies addressed to measure the pattern of expression of molecules involved in the pathogenesis of neurodegenerative and inflammatory diseases, such as neuropeptides and cytokines.

Animals↗

PubMed2000

Effect of interleukin-1beta on subdiaphragmatic vagal efferents in the rat.

Interleukin-1beta (IL-1beta) is an important mediator of fever and illness. Recent studies have demonstrated that IL-1beta (2 microg kg(-1)) increases gastric vagal afferent activity. The peripheral mechanisms of the action of lower doses were studied by recording the mass efferent and afferent activity of the gastric branch of the ventral vagal nerve in anesthetized rats. Twenty min after i.v. administration of IL-1beta (1 microg kg(-1)) the efferent activity of the vagal nerve was decreased to 62+/-6% in totally but not in partly vagotomized rats. Preadministration of indomethacin (5 mg kg(-1)) 30 min before IL-1beta blocked this reduction. Administration of 1 microg kg(-1) of IL-1beta had no effect on the afferent activity of the gastric branch of the vagal nerve. The present results suggest that the subdiaphragmatic vagal afferents modulate the parasympathetic efferent outflow in response to IL-1beta partly through prostaglandin dependent mechanisms and that supradiaphragmatic afferents or central sites are more sensitive to the low doses of IL-1beta which becomes evident after elimination of the subdiaphragmatic vagal input.

Animals↗

PubMed2000

Effects of galanin on wide-dynamic range neuron activity in the spinal dorsal horn of rats with sciatic nerve ligation.

Galanin is a 29-amino acid peptide with a suggested role in nociception. The effect of galanin on wide-dynamic range neuron discharge frequency in rats with nerve ligation, used as a model of neurogenic pain, was investigated by extracellular recording methods. Seven to 14 days after sciatic nerve ligation, 0.1, 0.5 or 1 nmol of galanin was administered directly on the dorsal surface of the L3-L5 spinal cord of rats with sciatic nerve ligation. It was found that galanin inhibited the activity of wide-dynamic range neurons dose-dependently, an effect was more pronounced in sciatic nerve ligated rats than intact rats. Furthermore, when 1 nmol of galantide, the galanin antagonist, was administered on the dorsal surface of the L3-L5 spinal cord, the wide-dynamic range neuron discharge frequency increased significantly. The results suggest that galanin plays an important role in the modulation of presumed nociception in mononeuropathy.

Animals↗

PubMed2000

Involvement of neuropeptide Y and Y1 receptor in antinociception in nucleus raphe magnus of rats.

The nociceptive response latencies increased significantly after intra-nucleus raphe magnus administration of 0.1 or 0.4 nmol of neuropeptide Y, but not 0.04 nmol, in rats. The neuropeptide Y-induced increases in hindpaw withdrawal latency were reversed by following injection of 0.42 nmol of the Y1 antagonist, NPY(28-36). The results indicate that NPY plays an antinociceptive role in nucleus raphe magnus in rats, which is mediated by the Y1 receptor. Furthermore, the neuropeptide Y-induced increases in hindpaw withdrawal latency were attenuated by following intra-nucleus raphe magnus injection of 6 nmol of the opioid antagonist naloxone, indicating that there is an interaction between NPY and opioids in nucleus raphe magnus.

Animals↗

PubMed2000

Effects of systemic injection of interleukin-1beta on gastric vagal afferent activity in rats lacking type A cholecystokinin receptors.

We have shown that systemic administration of interleukin-1beta (IL-1beta) excites gastric vagal afferent activity in part via stimulation of type A cholecystokinin (CCK-A) receptors in rats. The present study was undertaken to determine whether the response of the gastric vagal afferent nerve to systemic IL-1beta is altered in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which lack CCK-A receptors. The response was compared with that of the control strain, Long-Evans Tokushima Otsuka (LETO) rats. All animals were anesthetized with pentobarbital and artificially ventilated. Intravenous administration of 4 microg/kg of IL-1beta increased gastric vagal afferent activity in both LETO and OLETF rats, whereas a smaller dose of 2 microg/kg of IL-1beta increased activity only in the OLETF rats. The present results demonstrate that the response of the gastric vagal afferent activity in CCK-A receptor deficient OLETF rats was more sensitive to intravenous administration of IL-1beta than was in control LETO rats.

Animals↗

PubMed2000

Anti-nociceptive effects of calcitonin gene-related peptide in nucleus raphe magnus of rats: an effect attenuated by naloxone.

The present study investigated the role of calcitonin gene-related peptide (CGRP) on nociception in nucleus raphe magnus (NRM) and the interaction between CGRP and opioid peptides in NRM of rats. CGRP-like immunoreactivity was found at a concentration of 6.0+/-0. 77 pmol/g in NRM tissue of ten samples of rats, suggesting that it may contribute to physiological responses orchestrated by the NRM. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation increased significantly after intra-NRM administration of 0.5 or 1 nmol of CGRP in rats, but not 0.25 nmol. The anti-nociceptive effect induced by CGRP was antagonized by following intra-NRM injection of 1 nmol of the CGRP receptor antagonist CGRP8-37. Furthermore, the CGRP-induced anti-nociceptive effect was attenuated by following intra-NRM administration of 6 nmol of naloxone. The results indicate that CGRP and its receptors play an important role in anti-nociception, and there is a possible interaction between CGRP and opioid peptides in NRM of rats.

Animals↗

PubMed2000

Antinociceptive effects of calcitonin gene-related peptide injected into periaqueductal grey of rats with mononeuropathy.

Intra-periaqueductal grey (PAG) injection of calcitonin gene-related peptide (CGRP) induced dose-dependent increases in hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats with mononeuropathy. CGRP-induced increases in HWLs were blocked by intra-PAG injection of the CGRP antagonist CGRP8-37. The results demonstrated that CGRP and CGRP receptors in PAG play an important role in antinociception in rats with mononeuropathy.

Analgesia↗

PubMed2000

Antinociceptive effects induced by intra-periaqueductal grey administration of neuropeptide Y in rats.

Hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation increased dose-dependently after intra-periaqueductal grey (PAG) injection of neuropeptide Y (NPY). Furthermore, the NPY-induced increases in HWLs were attenuated by intra-PAG injection of the Y1 receptor antagonist NPY28-36. The results demonstrated that NPY plays an important role in antinociception in PAG, in which Y1 receptor is involved in.

Analgesia↗

PubMed2000

Central changes in nociceptin dynorphin B and Met-enkephalin-Arg-Phe in different models of nociception.

The newly identified neuropeptide nociceptin/orphanin FQ (NOC) was measured in different rat brain areas related to the descending anti-nociceptive pathways and compared to two opioid peptides, dynorphin B (DYN B) and Met-enkephalinArgPhe (MEAP). Two experimental models of chronic nociception, one neurogenic and one inflammatory, used in this study, reveal how different pathological conditions may influence these endogenous systems. Nerve injury is induced by ligation of the sciatic nerve and inflammation by a carrageenan injection in the gluteal muscle, 2 weeks prior to decapitation. Selected brain areas were dissected out and frozen. NOC-, DYN B- and MEAP-like immunoreactivity (LI) is determined by radioimmunoassay. Nerve injury increased the NOC-LI levels in the cortex cinguli, DYN B-LI levels in the dorsal and the ventral part of the spinal cord, whereas a decrease in the MEAP-LI levels is seen in the dorsal part of the periaqueductal grey (PAG). After inflammation, the NOC-LI levels increased in cortex cinguli, hypothalamus and in the dorsal spinal cord, whereas DYN B-LI levels increased in the dorsal part of the PAG. A general increase in MEAP-LI levels is found after inflammation in all analyzed brain areas except in hippocampus. In conclusion, increased levels of NOC-LI were found in cortex cinguli in both treatment groups and in hypothalamus and spinal cord following carrageenan treatment. The changes in the NOC-LI concentrations were not parallelled by changes in DYN B-LI and MEAP-LI, suggesting that NOC and opioid peptides elicit different reactions in the systems of nociception/antinociception.

Animals↗

PubMed2000

Contralateral treatment with xylocaine reduces nociceptive behaviour in mononeuropathic rats.

The aim of the present study was to establish whether contralateral treatment with local anaesthetics reduces nociceptive behaviour in mononeuropathic rats. Contralateral treatment with xylocaine on day 6 and 11 following sciatic nerve ligation increased withdrawal latencies to thermal but not to mechanical stimulation for 3-4 days. Rats who received contralateral treatment with xylocaine on day 6 and 11 showed a reduced autotomy score during the following 6 weeks. To compare ipsilateral and contralateral effects another set of experiments was performed. Rats treated contralaterally on day 11 had a significantly lower autotomy score at week 4 and 6. Our results demonstrate that contralateral treatment with xylocaine reduces nociceptive behaviour in mononeuropathic rats for days or weeks.

Anesthetics, Local↗

PubMed2000

An interaction of opioids and galanin in dorsal horn of the spinal cord in mononeuropathic rats.

The present study was performed in rats with experimentally induced mononeuropathy after common sciatic nerve ligation. The hind-paw withdrawal latencies to thermal and mechanical stimulation were increased significantly after intrathecal injection of 3 nmol of galanin. The increased hind-paw response latencies induced by galanin were attenuated by following intrathecal injection of 22 nmol, but not 11 or 2.75 nmol of the opioid receptor antagonist naloxone. Further, the increased hind-paw response latencies induced by galanin were prevented by following intrathecal injection of 10 nmol of mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), but not by 10 nmol of delta-opioid receptor antagonist, natrindole or 10 nmol of kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI). Intrathecal 10 nmol of beta-FNA alone had no significant effects on the hind-paw withdrawal responses. These results demonstrate the existence of a specific interaction between galanin and opioids in the transmission of presumed nociceptive information in the spinal cord of mononeuropathic rats. This interaction involves the activation of mu-opioid receptor.

Animals↗

PubMed2000

Interactions of galanin and morphine in the spinal antinociception in rats with mononeuropathy.

The increased hind-paw withdrawal latency (HWL) to thermal stimulation and hind-paw withdrawal threshold (HWT) to mechanical stimulation induced by morphine were attenuated by intrathecal injection of 1 or 3 nmol, but not 0.3 nmol of the selective galanin antagonist galantide. The result indicated a possible interaction between galanin and opioids in the transmission of presumed nociceptive information in the spinal cord of rats with mononeuropathy.

Analgesics, Opioid↗

PubMed2000

Effect of propranolol and granisetron on experimentally induced pain and allodynia/hyperalgesia by intramuscular injection of serotonin into the human masseter muscle.

We have previously reported that intramuscular injection of serotonin (5-HT) into the masseter muscle elicits pain and allodynia/hyperalgesia in healthy subjects. The aim of this study was to investigate whether the 5-HT(3) receptor antagonist granisetron or 5-HT(1A) receptor antagonist propranolol can reduce 5-HT induced pain and allodynia/hyperalgesia in the masseter muscle. Twenty-four healthy individuals (12 males and 12 females) without pain from the masseter muscle region participated. They were examined clinically including tenderness to digital palpation (TDP) and pressure pain threshold (PPT) of the masseter muscle. 5-HT in combination with granisetron or propranolol was randomly injected on one side in a double-blind manner. 5-HT in combination with saline was used on the contralateral side. After the injections the pain intensity and PPT were recorded 10 times during 30min. After the last recording the TDP was assessed again. The injections were repeated with the other antagonist within 1 week. All three combinations of substances elicited pain after injection, which lasted for 5-8min. 5-HT induced significantly more pain than granisetron+5-HT and propranolol+5-HT. The TDP increased significantly after injection of all combinations of substances, but there was no significant difference between them. The PPT decreased significantly after injection of 5-HT and increased significantly after injection of granisetron+5-HT, while it did not change significantly after injection of propranolol+5-HT. The difference between 5-HT and granisetron+5-HT was significant. In conclusion, the results of this study indicate that injection of granisetron and propranolol into the human masseter muscle reduces pain induced by local administration of 5-HT, but that the effect of granisetron is stronger than that of propranolol. In addition, granisetron totally abolishes allodynia/hyperalgesia.

Adult↗

PubMed2000

Pain and allodynia/hyperalgesia induced by intramuscular injection of serotonin in patients with fibromyalgia and healthy individuals.

The aim of this study was to investigate the effect of injection of serotonin (5-HT) into the masseter muscle on pain and allodynia/hyperalgesia. Twelve female patients with fibromyalgia (FM) and 12 age-matched female healthy individuals (HI) participated in the study. The current pain intensity (CPI) and the pressure pain threshold (PPT) of the superficial masseter muscles were assessed bilaterally. 5-HT in one of three randomized concentrations (10(-3), 10(-5), 10(-7) M) or isotonic saline was then injected into either of the two masseter muscles in a double-blind manner. After the injections the CPI and PPT were recorded ten times during 30 min. The injections were repeated twice with the other concentrations of 5-HT after 1 and 2 weeks, respectively. In the FM-group there was a non-significant increase of CPI after injection that lasted during the entire 30-min period irrespective of whether 5-HT or saline was injected. Neither did the PPT change significantly. In the HI-group pain developed significantly after injection irrespective of whether 5-HT or saline was injected, but significantly more so after 5-HT at 10(-3) M than saline injection. CPI decreased quickly and then remained on a very low level for most of the experiment. 5-HT at both 10(-5) M and 10(-3) M caused a significantly greater decrease of PPT than saline. In conclusion, our results show that 5-HT injected into the masseter muscle of healthy female subjects elicits pain and allodynia/hyperalgesia, while no such responses occur in patients with fibromyalgia.

Adult↗

PubMed2000

Antinociceptive role of galanin in periaqueductal grey of rats with experimentally induced mononeuropathy.

The present study was performed in rats with experimentally induced mononeuropathy after left common sciatic nerve ligation. The hindpaw withdrawal latencies to thermal and mechanical stimulation increased significantly after intra-periaqueductal grey injection of 2 or 3nmol, but not 1nmol of galanin in rats with mononeuropathy. Intraperitoneal administration of 4.5mg/kg morphine induced significant increases in hindpaw withdrawal latencies to both noxious stimulation, which were attenuated by following intra-periaqueductal grey injection of 2nmol of the galanin antagonist galantide. Furthermore, the antinociceptive effect induced by intra-periaqueductal grey injection of 26.6nmol of morphine was attenuated significantly by following intra-periaqueductal gray administration of 2nmol of galantide. The results demonstrated that in periaqueductal grey galanin plays an antinociceptive role in rats with mononeuropathy and galanin is involved in the mechanisms of opioid-induced antinociception.

Analgesics↗

PubMed2000

Cholecystokinin-8 enhances nerve growth factor synthesis and promotes recovery of capsaicin-induced sensory deficit.

Alterations of nerve growth factor (NGF) expression have been demonstrated during peripheral nerve disease and the impaired expression or synthesis and transportation of NGF has been correlated with the pathogenesis of several peripheral neuropathies. Since exogenous NGF administration seems to cause undesired side-effects, therapeutical strategies based on the regulation of endogenous synthesis of NGF could prove useful in the clinical treatment of these disorders. The aim of the present study was to analyse the effects of exogenous peripheral administration of the neuropeptide cholecystokinin-8 (CCK-8) on endogenous NGF synthesis, NGF mRNA and distribution of peripheral neuropeptides which are known to be regulated by this neurotrophin. To address these questions we studied the effects of capsaicin (CAPS) before and after the administration of CCK-8 on NGF levels, NGF mRNA expression and localization, and the concentration of substance P (SP) and calcitonin gene-related peptide (CGRP) in peripheral tissue These studies demonstrate that administration of the CCK-8 induces an increase of NGF protein and mRNA in peripheral tissue. NGF level in paw skin of CAPS/CCK-8-treated mice is 3 fold higher than in controls (1241+/-110 pg gr(-1) of tissue wet weight versus 414+/-110 pg gr(-1) of controls) and nearly 6 fold higher than in CAPS-treated mice (1241+/-110 pg gr(-1) versus 248+/-27 pg gr(-1)). The increase of NGF is correlated with the recovery of impaired nocifensive behaviour and with an overexpression of SP and CGRP. The evidence that CCK-8 promotes the recovery of sensory deficits suggests a potential clinical use for this neuropeptide in peripheral neuropathies.

Animals↗

PubMed2000

Exogenous cholecystokinin-8 reduces vagal efferent nerve activity in rats through CCK(A) receptors.

It has been proposed that the vagus nerve plays a role in mediating cholecystokinin-8 (CCK-8) effect on such gastric functions as motility, emptying and gastric acid secretion. To examine the contribution of the efferent pathways in realizing these effects, efferent mass activity in the ventral gastric vagal nerve in Sprague-Dawley rats was recorded. Intravenous infusion of CCK-8 (0.1-1 nmol) suppressed the efferent activity. The effect of CCK-8 was significantly reduced in animals with total subdiaphragmatic vagotomy in comparison to those with partial vagotomy. Intravenous infusion of CCK(A) receptor antagonist L-364,718 (1-100x10(-6) g) blocked the response of vagal efferent activity to 0.1 nmol CCK-8, but the CCK(B) receptor antagonist L-365,260 (1-100x10(-6) g) did not in the conditions of either partial or total vagotomy. Intracisternal infusion of L-364,718 (1x10(-6) g) blocked the response of vagal efferent activity to 0.1 nmol CCK-8 i.v. Infusion of exogenous CCK-8 did not affect the activity of supradiaphragmatic vagal afferents. The results suggest that the effect of systemically administered CCK-8 on vagal efferent activity is mediated by both peripherally (subdiaphragmatically) and centrally localized CCK(A) receptors.

Animals↗