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Biomedical subjects

T Lundeberg

Publications and source records attributed to T Lundeberg.

At least 145 records · Page 8Linked to original sources

Significant changes in neuropeptide concentrations in the brain of normotensive (WKY) and spontaneously hypertensive (SHR) rats following knee joint monoarthritis.

Changes induced by chronic monoarthritis in the nervous system was studied by measuring concentrations of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivities in the brain and in the knee joints of control and monoarthritic normotensive (WKY) and spontaneously hypertensive (SHR) rats on day 21 after the induction of monoarthritis. Knee joint monoarthritis was induced by intra-articular injection of Freund's adjuvant into the right knee joint. The severity of arthritis was examined by measuring knee volumes and scratching behaviour and by X-ray. The right knee of both WKY and SHR monoarthritic rats had an increased volume and osteoporosis. SHR rats had more severe arthritis and increased scratching behaviour compared to the WKY. Tachykinins were significantly decreased in the hypothalamus of arthritic rats. In the pituitary higher concentrations of tachykinins and CGRP were found in the arthritic and/or control SHR rats than in the WKY. In the occipital cortex, striatum and hippocampus NPY was increased in monoarthritic rats. No correlation was found between neuropeptide concentrations in the brain and knee joints. Decrease of tachykinins and increase of CGRP to different degree in the hypothalamus and/or pituitary of the arthritic WKY and SHR rats indicates that these changes were selectively associated with the basal level of sympathetic tone and possibly related to the greater severity seen in SHR rats. The increase of NPY in the brain, not influenced by sympathetic tone, may be part of a general defence reaction to inflammation.

Animals↗

Monosodium glutamate increases NGF and NPY concentrations in rat hypothalamus and pituitary.

The effects of MSG treatment on NGF and NPY levels were analysed in the hypothalamus, pituitary, adrenal, thyroid and testis of adult rats. Daily i.v. injections of MSG (1 g kg-1 for 1 week) induced an increase of NGF in the hypothalamus (control (C) = 378 +/- 54; saline (S) = 369 +/- 36; MSG = 479 +/- 35 pg g-1 tissue; p < 0.001) and pituitary (C = 310 +/- 34; S = 376 +/- 114; MSG = 576 +/- 98 pg g-1 tissue; p < 0.01). Hypothalamic and pituitary NPY concentrations were also altered in the MSG-treated rats. Compared with saline-treated rats, the NPY concentration increased by 43% in the hypothalamus and 37.5% in the pituitary of MSG-treated rats. No significant changes in NGF and NPY content were found in the adrenal or thyroid of treated animals. These results suggest that hypothalamic and pituitary NGF and NPY levels may be involved in the control of neuroendocrine functions that are affected by MSG treatment.

Animals↗

Massage-like stroking of the abdomen lowers blood pressure in anesthetized rats: influence of oxytocin.

The aim of this study was to determine how massage-like stroking of the abdomen in rats influences arterial blood pressure. The participation of oxytocinergic mechanisms in this effect was also investigated. The ventral and/or lateral sides of the abdomen were stroked at a speed of 20 cm/s with a frequency of 0.017-0.67 Hz in pentobarbital anesthetized, artificially ventilated rats. Arterial blood pressure was recorded with a pressure transducer via a catheter in the carotid artery. Stroking of the ventral, or both ventral and lateral sides of the abdomen for 1 min with a frequency of 0.67 Hz caused a marked decrease in arterial blood pressure (approx. 50 mmHg). After cessation of the stimulation blood pressure returned to the control level within 1 min. The maximum decrease in blood pressure was achieved at frequencies of 0.083 Hz or more. Stroking only the lateral sides of the abdomen elicited a significantly smaller decrease in blood pressure (approx. 30 mmHg decrease) than stroking the ventral side. The decrease in blood pressure caused by stroking was not altered by s.c. administration of an oxytocin antagonist (1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin, 1 mg/kg) directed against the uterine receptor. In contrast, the administration of 0.1 mg/kg of oxytocin diminished the effect, which was antagonized by a simultaneous injection of the oxytocin antagonist. These results indicate that the massage-like stroking of the abdomen decreases blood pressure in anesthetized rats. This effect does not involve intrinsic oxytocinergic transmission. However, since exogenously applied oxytocin was found to diminish the effect of stroking, oxytocin may exert an inhibitory modulatory effect on this reflex arc.

Abdomen↗

Opioid antagonists naloxone, beta-funaltrexamine and naltrindole, but not nor-binaltorphimine, reverse the increased hindpaw withdrawal latency in rats induced by intrathecal administration of the calcitonin gene-related peptide antagonist CGRP8-37.

We recently demonstrated that intrathecal administration of calcitonin gene-related peptide 8-37 (CGRP8-37), a selective antagonist of calcitonin gene-related peptide receptors, dose-dependently increased the latency to hindpaw withdrawal responses induced by both thermal and mechanical stimulation in intact rats, indicating a role for CGRP and its receptors in the transmission of presumed nociceptive information in the spinal cord. The present study was performed to explore the interaction between CGRP and opioids in the spinal cord of rats. The effects of naloxone, a non-selective opioid receptor antagonist, and three different selective opioid receptor antagonists on the increased latency to withdrawal response induced by intrathecal injection of CGRP8-37 were explored. Intrathecal administration of 10 nmol of CGRP8-37 induced a significant bilateral increase in hindpaw withdrawal latency to both thermal and mechanical stimulation. The effect was partly reversed by intrathecal injection of 4 or 8 micrograms of naloxone, 10 nmol of either the mu opioid receptor antagonist beta-funaltrexamine or the delta opioid receptor antagonist naltrindole, but not by 10 nmol of the kappa opioid receptor antagonist nor-binaltorphimine. These results indicate that mu and delta, but not kappa, opioid receptors are involved in the modulation of post-synaptic effects and/or release of CGRP and other neurotransmitters.

Animals↗

Changes of neuropeptide concentrations in the brain following experimentally induced mononeuropathy in Wistar Kyoto and spontaneously hypertensive rats.

The effect of unilateral, experimentally induced, mononeuropathy on concentrations of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP), calcitonin gene-related peptide CGRP) and galanin- (GAL-) like immunoreactivities (-LI) was studied in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rat brains. Two weeks following ligation of the sciatic nerve, significantly higher concentrations of NPY-LI were found in the hippocampus, striatum and occipital cortex of both rat strains. CGRP-LI and GAL-LI were increased in the hippocampus of WKY rats. NKA-LI and SP-LI were decreased to different degrees in the pituitary of the WKY and SHR rats, indicating that the changes of the tachykinins, CGRP and GAL were selectively associated with the basal level of sympathetic tone. The increased concentrations of NPY-LI in the brain, not influenced by sympathetic tone, may be part of a general defense reaction in response to trauma.

Animals↗

The oxytocin antagonist 1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin reverses the increase in the withdrawal response latency to thermal, but not mechanical nociceptive stimuli following oxytocin administration or massage-like stroking in rats.

In this study the effect of exogenous oxytocin and of massage-like stroking on the withdrawal latency responses to heat and mechanical nociceptive stimulation were investigated in rats. A hot-plate test and the Randall-Selitto test were used to assess the withdrawal responses. Exogenous oxytocin (0.1-1 mg/kg) and stroking (a low frequency mechanical stimulation) significantly increased the withdrawal latencies in response to mechanical and to thermal nociceptive stimuli. The effect of oxytocin and of stroking in the hot-plate test was reversed by the oxytocin antagonist (1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin) directed against the uterine receptor. In contrast, the antagonist did not affect the prolonged response latency in the mechanical nociceptive stimulation test following either exogenous oxytocin or stroking. These results support the view that (1) oxytocin administration affects directly or indirectly nociceptive related behaviour in response to heat stimulation, and (2) massage-like stroking may have an anti-nociceptive effect via activation of oxytocinergic mechanisms. Since the response to mechanical stimulation was not blocked by the antagonist the mechanisms mediating the withdrawal latency to heat and mechanical stimulation could be different.

Animals↗

Capsaicin effects on substance P and CGRP in rat adjuvant arthritis.

The effects of capsaicin on the sensory neuropeptides substance P and calcitonin gene-related peptide were analyzed in the ankle joints and dorsal root ganglia (L2-L6) of adult female Lewis rats. The study included 23 normal rats and 23 arthritic rats, all injected subcutaneously with capsaicin (total dose 200 mg/kg bw). Another two groups of animals from a previous study, i.e., 23 normal rats and 23 arthritic rats not given capsaicin served as controls. Adjuvant arthritis was induced by inoculation with heat-killed mycobacteria. The morphological distribution of sensory neuropeptides was assessed by immunohistochemistry and the tissue concentrations were determined by radioimmunoassay. In normal rats, capsaicin significantly reduced the concentrations of substance P and calcitonin gene-related peptide in ankle joints (54 and 36%, respectively) as well as dorsal root ganglia (40 and 54%, respectively). In arthritic rats those pretreated with capsaicin had significantly lower concentrations of substance P and calcitonin gene-related peptide in dorsal root ganglia (19 and 42%, respectively) compared to the arthritic controls. In the ankle joints, however, only the SP concentration was reduced (42%). Notably, this was accompanied by a 40% reduction in inflammatory response as assessed by comparing the ankle joint weights of the experimental groups. In general, there was a good correlation between the neuropeptide concentrations in ipsilateral ankle joints and the corresponding dorsal root ganglia as assessed in individual rats. The present study of adjuvant induced arthritis shows that capsaicin administration reduces the otherwise up-regulated levels of sensory neuropeptides in dorsal root ganglia and ankle joints. However, capsaicin at the dose given can only mitigate, not completely prevent the development of joint inflammation. Nonetheless, the findings suggest that antineuronal therapy targeted against specific neurotransmitters may prove useful in inflammatory joint disease.

Animals↗

Severe peripheral ischemia after vasospasm may be prevented by spinal cord stimulation. A preliminary report of a study in a free-flap animal model.

Electric spinal cord stimulation (SCS) is at present used in many centers to treat ischemic pain and ischemia in peripheral vascular disease. The most promising results have been obtained in cases where a vasospastic component is dominating. The knowledge concerning the mechanisms behind these effects has been scanty, but recent experimental studies indicate that suppression of sympathetic activity and the release of vasoactive substances may be important. A problem with many of the animals studies aimed at exploring these mechanisms is that they have almost exclusively been performed on normal animals without ischemia. However, in studies of the responsiveness of local ischemia to various pharmacological substances and to electrical transcutaneous nerve stimulation, animal models with ischemic skin flaps have been used. We applied SCS via chronically implanted electrodes in a model of local vasospasm in the rat, induced by mechanical stimulation of the vessel supplying an island flap in the groin. Male Sprague-Dawley rats were used. First, a monopolar system for spinal cord stimulation, with the intraspinal cathode at vertebral level T11, was implanted in halothane anaesthesia. After about three days of recovery the rats were anaesthetized with chloral hydrate ip and a groin neurovascular flap based on the epigastric vessels was raised. Microcirculation in the flap as well as in a control area in the contralateral groin was monitored by laser Doppler technique. Vasospasm was induced by gently pinching the superficial epigastric artery with microforceps. Two groups of animals were submitted to two spasm periods, one with SCS applied for 20 min. by 50 Hz; 0.2 msec and with 2/3 of the intensity required for a motor response before the first period. The second group, receiving sham SCS, served as a control. Both degree of ischemia after spasm provocation and the time to recovery were evaluated. In general SCS affected basal flow very little. In the control group the rats demonstrated increasing vasospastic reactions with subsequent flap ischemia to the two mechanical provocations. In the experimental group a response pattern emerged indicating that pre-spasm SCS could both reduce the spasm amplitude and significantly shorten the time for restoration of a satisfactory microcirculation in the flap. Some few trials with pharmacologically induced spasm by topical application of noradrenaline onto the feeding vessel also followed the same pattern. In conclusion, SCS seems to be able to reduce vasospasm, especially if the treatment is given before the ischemic period. This approach may supply an animal model for further studies of possible mechanisms behind the microcirculatory effects of SCS.

Animals↗

Co-variation of neuropeptide Y, calcitonin gene-related peptide, substance P and neurokinin A in joint fluid from patients with temporomandibular joint arthritis.

Forty-one patients (37 female and four male) with signs and symptoms of temporomandibular joint arthritis, were separated into two diagnostic groups (group I: inflammatory; group II: degenerative/non-specific joint disease). They were examined clinically, fluid was aspirated from the joint with saline and venous blood samples were collected at the same time. The joint fluid and plasma samples were analysed for neuropeptide-like immunoreactivity, i.e. neuropeptide Y (NPY-LI), calcitonin gene-related peptide (CGRP-LI), substance P (SP-LI) and neurokinin A (NKA-LI), using competitive radioimmunoassays. The aim was to investigate any co-variation of the peptides in the joint fluid and plasma. In group I, the median values of peptide concentrations in joint fluid were SP-LI = 129, CGRP-LI = 75, NKA-LI = 36 and NPY-LI = 676 pmol/l and in group II, SP-LI = 52, CGRP-LI = 64, NKA-LI = 45 and NPY-LI = 318 pmol/l. There were no significant differences between the groups for peptide concentrations. In group I, all the neuropeptides were strongly correlated. In group II, SP-LI and NKA-LI were strongly correlated while CGRP-LI was weakly correlated with NPY-LI and NKA-LI. Multiple step-wise regression analysis showed that most of the variation in NPY-LI, CGRP-LI and SP-LI in group I was explained by NKA-LI, but the regression did not reach statistical significance in group II.

Adult↗

Acupuncture--from empiricism to science: functional background to acupuncture effects in pain and disease.

Acupuncture is part of Traditional Chinese Medicine, a system with an empirical basis which has been used in the treatment and prevention of disease for centuries. A lack of scientific studies to prove or disprove its claimed effects led to rejection by many of the western scientific community. Now that the mechanisms can be partly explained in terms of endogenous pain inhibitory systems, the integration of acupuncture with conventional medicine may be possible. Its use for pain relief has been supported by clinical trials and this has facilitated its acceptance in pain clinics in most countries. Acupuncture effects must devolve from physiological and/or psychological mechanisms with biological foundations, and needle stimulation could represent the artificial activation of systems obtained by natural biological effects in functional situations. Acupuncture and some other forms of sensory stimulation elicit similar effects in man and other mammals, suggesting that they bring about fundamental physiological changes. Acupuncture excites receptors or nerve fibres in the stimulated tissue which are also physiologically activated by strong muscle contractions and the effects on certain organ functions are similar to those obtained by protracted exercise. Both exercise and acupuncture produce rhythmic discharges in nerve fibres, and cause the release of endogenous opioids and oxytocin essential to the induction of functional changes in different organ systems. Beta-endorphin levels, important in pain control as well as in the regulation of blood pressure and body temperature, have been observed to rise in the brain tissue of animals after both acupuncture and strong exercise. Experimental and clinical evidence suggest that acupuncture may affect the sympathetic system via mechanisms at the hypothalamic and brainstem levels, and that the hypothalamic beta-endorphinergic system has inhibitory effects on the vasomotorcenter, VMC. Post-stimulatory sympathetic inhibition which proceeds to a maximum after a few hours and can be sustained for more than 12 hours, has been demonstrated in both man and animals. Experimental and clinical studies suggest that afferent input in somatic nerve fibres has a significant effect on autonomic functions. Hypothetically, the physiological counterpart lies in physical exercise, and the effect can be artificially reproduced via various types of electrical or manual stimulation of certain nerve fibres.

Acupuncture Therapy↗

Calcitonin gene-related peptide increases microcirculation after mechanically induced ischemia in an experimental island flap.

Vasoconstriction, as a result of mechanical manipulation of blood vessels during microsurgery, may produce a decrease in blood supply and endanger flap viability. A study was undertaken to determine the effects of the topical vasodilator calcitonin gene-related peptide on the microcirculation of flaps after mechanically induced ischemia. A neurovascular island flap based on the superficial epigastric vessels was raised in 42 rats. Blood cell flux in the flap was recorded continuously with a laser Doppler flux meter. The feeding artery was pinched to induce vasospasm, and different concentrations of calcitonin gene-related peptide (10(-7), 10(-8), 10(-9), 10(-10) mol) or a control of sodium chloride 0.9% was applied topically to relieve the ischemia. Results showed that calcitonin gene-related peptide at a concentration of 10(-7) mol significantly shortened the time to reach 50% of the original blood cell flux values (270 +/- 123 seconds) and significantly increased the number of flaps in which the blood cell flux values were restored to prestress levels within 30 minutes. The data support the conclusion that, in this model, topical calcitonin gene-related peptide at the concentration of 10(-7) mol was effective in promoting recovery of the microcirculation after mechanically induced ischemia, without the adverse effects associated with other commonly used vasodilators.

Animals↗

A nonconventional approach to the treatment of "environmental illness".

Twenty patients with symptoms of "environmental illness" were subject to a controlled study of deep versus superficial acupuncture. The patients were evaluated by a detailed questionnaire concerning their occupational, environmental, and medical history. Blood samples were taken as well. Patients were randomized to deep or superficial acupuncture. Both groups improved significantly in key variables during and after treatment. There were no group differences. There were no changes in biological variables apart from a gradual and continuous increase in serum cortisol and a decrease in neuropeptide Y, which was somewhat more accentuated in those receiving deep acupuncture. This rise in cortisol may have contributed to decreased dermal symptoms among the participants. It is hypothesized that the positive treatment results observed are partly due to weakening of the conditioned response, linking bodily symptoms to environmental agents. To date, a number of different methods have been tried in the management of patients with environmental illness. However, only rarely have the treatments been evaluated in controlled studies.

Acupuncture Therapy↗

Determination of temporomandibular joint fluid concentrations using vitamin B12 as an internal standard.

The aim of the investigation was to test the reproducibility and accuracy of a new method to measure temporomandibular joint (TMJ) fluid concentrations of various substances by saline washing, using exogenous B12 as a marker. An in vitro test was first performed with glucose as a test substance. The difference between a B12-calculated and known standard concentration of glucose was very small. Saline washing of the TMJ was performed on 13 patients having signs of TMJ arthritis, and the aspirates obtained were analyzed for neuropeptide Y-like immunoreactivity (NPY-LI) and interleukin-1 beta (IL-1 beta). Vitamin B12 was mixed with the saline immediately before injection, and a sample of the aspirate was later compared photometrically with the injection solution. There were positive correlations between saline aspirate and joint fluid concentrations for NPY-LI and IL-1 beta, and the correlations were stronger for saline aspirates with high joint fluid content. This study shows that the method is reliable for measurement of joint fluid concentrations of various substances, such as NPY-LI and IL-1 beta.

Arthritis↗

Preemptive spinal cord stimulation reduces ischemia in an animal model of vasospasm.

Spinal cord stimulation (SCS) has been increasingly used in the treatment of ischemia caused by obliterative diseases in the extremities and in the cardiac circulation. The most promising effects have been obtained when physicians suspect that a major vasospastic component underlies the ischemic symptoms (e.g., as in Raynaud's disease). Despite the clinical success of this treatment method, little is known about the mechanisms underlying the pain relief it produces and its anti-ischemic effects. Most earlier experimental studies have used normal animals or animals with cerebral vasospasm induced by injection of autologal blood into the cerebrospinal fluid space. In the present study, we applied SCS in a rat model via implanted electrodes to study the effect of preemptive stimulation on the ischemia caused by vasospasm in a neurovascular flap in the groin; the vasospasm was induced by mechanical pressure applied to the feeding artery. In rats treated with SCS, delivered with parameters similar to those used clinically, the percentage of flaps recovering normal microcirculation after the spasm was significantly higher than in the untreated control group (100 and 28%, respectively; P < 0.05), and the maximal blood flow after the ischemic episode was significantly higher in the SCS group than in the control group (127 and 51 arbitrary units, respectively; P < 0.05). The percentage of animals regaining the premanipulation circulation after the provocation of a second spasm was also greater in the SCS-treated group than in the control animals (50 and 14%, respectively; P < 0.05). Pilot studies showed that this protective effect was specific to SCS given before spasm induction, an observation corroborated by clinical experiences.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neuropeptides in the arthritic TMJ and symptoms and signs from the stomatognathic system with special consideration to rheumatoid arthritis.

The contribution of the nervous system to the pathophysiology of rheumatoid arthritis has been proposed to be mediated by certain neuropeptides. Neuropeptide Y, calcitonin gene-related peptide, substance P, and neurokinin A are considered modulators of inflammatory joint disease. Parameters of pain, as well as occlusal signs of tissue destruction from the arthritic TMJ and the corresponding neuropeptide concentrations in TMJ synovial fluid, were investigated in patients with various inflammatory joint diseases. The patients with rheumatoid arthritis were also examined in a separate diagnostic group. Visual analog scale, palpatory tenderness, maximal voluntary mouth opening, and anterior open bite were correlated to neuropeptide-like immunoreactivities of the above four neuropeptides. It was found that high concentrations of calcitonin gene-related peptide and neuropeptide Y in TMJ fluid are associated with pain, impairment of mandibular mobility, and occlusal signs of TMJ destruction in patients with rheumatoid arthritis. The results indicated neuropeptide involvement in rheumatoid arthritis, proposing a potentiation of the symptoms and signs by the inflammatory action of calcitonin gene-related peptide and neuropeptide Y.

Adult↗

Effects of electro-acupuncture and physical exercise on regional concentrations of neuropeptides in rat brain.

The effects of single or repeated treatments with manual acupuncture (ACU), electro-acupuncture (ELACU) or physical exercise on neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP), galanin (GAL) and vasoactive intestinal peptide (VIP)-like immunoreactivity (-LI) in different regions of the rat brain were studied. Initially the effect of microwave irradiation (MWI) was compared to decapitation on the recovery of neuropeptides, and significantly higher concentrations of SP-LI, NKA-LI and NPY-LI were found in the hippocampus, occipital cortex, pituitary and striatum following MWI. Repeated ELACU treatments significantly increased SP-LI, NKA-LI and NPY-LI in the hippocampus and NPY-LI in the occipital cortex. No changes were found in animals receiving ACU or performing physical exercise.

Acupuncture Therapy↗