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Biomedical subjects

T Lundeberg

Publications and source records attributed to T Lundeberg.

At least 73 records · Page 4Linked to original sources

Effects of intrathecal galanin on nociceptive responses in rats with mononeuropathy.

The present study was performed on rats with experimental mononeuropathy induced by left common sciatic nerve loose ligation. Unilateral sciatic nerve loose ligation induced decreases of the hindpaw withdrawal latency to the hot-plate test, cold-plate test and the Randall Selitto test. Sciatic nerve loose ligation induced hyperesponsiveness to touch at room temperature also. Intrathecal administration of either 3 or 6 nmol of galanin, but not 1 nmol, induced significant bilateral increases in hindpaw withdrawal latencies to the hot-plate test, cold-plate test and the Randall Selitto tests in rats with left mononeuropathy. The results indicate that galanin may play important roles in transmission of presumed nociceptive information in the spinal cord of mononeuropathic rats.

Animals↗

Behavioural anxiolytic effects of low-dose anabolic androgenic steroid treatment in rats.

The use of anabolic androgenic steroids (AAS) in supratherapeutic doses has been associated with aggressive behaviour as well as with severe affective and psychotic symptoms. These symptoms usually follow a chronic exposure for several months. However, AAS also may have milder effects with hypomania-like features such as an increase in confidence, energy and self-esteem. We have studied the short-term effects on male rat behaviour in a modified open-field test of the AAS Metenolon administered three times at a low dose (0.01 mg/kg/week x 3). The control rats showed indications of increased timidity and aversive learning following retesting, a reaction that was absent in the AAS-treated rats. The AAS-treated rats showed less fear or anticipatory anxiety compared to control animals. Furthermore, the suppressed marking behaviour and altered morphological allometric relationships were compatible with a modified social and sexual competence in the AAS treated rats.

Agonistic Behavior↗

Inhibitory effects of tachykinin receptor antagonists on thermally induced inflammatory reactions in a rat model.

Recent studies have proposed that activation of the sensory nervous system after thermal injury induces the release of vasoactive neuropeptides, including tachykinins which contribute to the local inflammatory reaction as well as to the nociceptive transmission at the spinal cord level. Effects of the tachykinins substance P and neurokinin A are mediated by the neurokinin 1 and 2 (NK1, NK2) receptors. The aim of the present study was to investigate the modulatory role of NK1 and NK2 antagonists on edema formation, and on hindpaw withdrawal latency to experimentally asses nociception. Thermal injury was inflicted on the anaesthetized rat by dipping the right hindpaw into hot water at 60 degrees C for 20 s. The amount of edema formation was calculated by measuring the hindpaw volume with a plethysmograph before and during 420 min after scalding. In other studies scalding was inflicted under brief anesthesia, and hindpaw withdrawal latencies (HWL) to mechanical stimulation were recorded before injury and at 180 min after. The effect on edemic reactions of rats treated locally with NK1 and NK2 receptor antagonist were studied, as well as the effect of the same compounds on HWL after intrathecal injection. Scalding induced a progressive edema formation which was reduced significantly in rats treated with local injection of 100 nmol of NK1 and NK2 antagonists 45 min after the injury. The thermally induced inflammation was followed by significant decrease of the latency of hindpaw withdrawal response to mechanical stimulation. Intrathecal injection of 30 nmol of the same drugs 180 min after scalding was followed by significant increase in HWL. The results indicate that SP and NKA contribute to the inflammatory reactions after thermal injury and that the tachykinin receptor antagonists possess the ability to reduce both the local edemic reaction as well as the nociceptive transmission at the spinal cord level.

Animals↗

Effects of calcitonin gene-related peptide on tissue survival, blood flow and neutrophil recruitment in experimental skin flaps.

Local administration of calcitonin gene-related peptide (CGRP) has been shown to improve tissue survival in surgical skin flaps. Moreover, topical CGRP has been demonstrated to exert anti-inflammatory effects in different animal models of skin inflammation. The aim of the present study was to establish whether systemic treatment with low doses of CGRP may improve survival and reduce neutrophil accumulation in surgical skin flaps. Using a well-established dorsal skin-flap model in the rat, we found that intraperitoneal (i.p.) pretreatment with low doses of CGRP dose-dependently increased flap survival. Thus, in untreated animals flap survival at day 7 after surgery was 42%, as compared to 44%, 60%, 69% and 73% survival after a single preoperative i.p. injection of 10(-15), 10(-12), 10(-9) and 10(-6) mol CGRP, respectively (P < 0.05 versus control for the three highest doses). The three effective doses had no detectable effects on either flap blood flow (laser Doppler) or mean arterial blood pressure. On the other hand, 5 x 10(-9) mol CGRP i.p. significantly reduced the marked surgery-induced accumulation of flap myeloperoxidase (a marker for neutrophil recruitment) without affecting the circulating neutrophil count. Taken together, our findings demonstrate that low systemic doses of CGRP can cause a major improvement in skin-flap survival in the rat, possibly via inhibition of surgically induced neutrophil recruitment.

Animals↗

Exercise and variations in neuropeptide concentrations in rheumatoid arthritis.

The aim of the present study was to investigate the influence of an exercise program on neuropeptide concentrations, disease activity, impairments and disabilities in rheumatoid arthritis (RA). Eleven females (median age 60 years, median disease duration 6.5 years, ARA functional classes I or II) exercised 30 min daily for 4 weeks. The urine concentrations of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and neuropeptide Y-like immunoreactivity (NPY-LI) were analyzed 1 week prior to exercise start, at exercise start, after 2 and 4 weeks of exercise, and after a 4-week follow-up period. Measurements of disease activity, aerobic capacity, grip force, limb muscle function, and activities of daily living (ADL) were also undertaken. The results indicate a decrease (md 5.64 pM to md 3.48 pM, P</=0.05) of CGRP-LI concentrations after 4 weeks' exercise. NPY-LI concentrations remained unchanged, as did disease activity and aerobic capacity. Muscle function and ADL capacity improved significantly (P</=0.05) after the exercise period. Only the improved grip force remained after the follow-up period. In conclusion the results indicate that decreased CGRP-LI concentration, probably reflecting a decreased sympathetic tone, follows physical exercise and suggest that regular physical activity might be important among individuals with RA to maintain a decreased sympathetic tone and less symptoms from their disease.

Adult↗

Sensory stimulation (acupuncture) increases the release of calcitonin gene-related peptide in the saliva of xerostomia sufferers.

Over the last decade, several patients afflicted with xerostomia have been treated with acupuncture. Their salivary flow rates increased significantly and the improvement lasted during a long observation period. We also found that the release of several neuropeptides in the saliva of healthy subjects can be increased by acupuncture stimulation. The concentration of vasoactive intestinal polypeptide increased significantly in the saliva of xerostomic patients after acupuncture treatment. The release of the neuropeptide calcitonin gene-related peptide (CGRP) was investigated in the saliva of xerostomic patients in order to elucidate further the mechanisms of the effect of sensory stimulation (acupuncture) on the salivary secretion. CGRP-like immunoreactivity was measured with radioimmunoassay (RIA) before and after a double series of acupuncture treatment, in stimulated saliva of 14 patients who suffered from xerostomia. The results showed that the concentration of CGRP increased significantly (P<0.001) in the saliva of these patients after the end of acupuncture treatment as compared to base-line levels. Taking into consideration the influence of CGRP on the salivary flow, as well as its trophic effect, we concluded that the increased release of CGRP could be one of the factors that affect positively the salivary flow rates of xerostomic patients who were treated with acupuncture.

Acupuncture Therapy↗

Dexamethasone increases survival and attenuates induction of inducible nitric oxide synthase in experimental skin flaps.

The molecule nitric oxide synthesized by the enzyme nitric oxide synthase (NOS) has been shown to be of major physiological and pathophysiological importance in the body. During ischemia and reperfusion, induction of free ionic calcium (Ca2+)-independent inducible NOS (iNOS) is thought to result in an overproduction of NO, leading to tissue damage. The glucocorticoid dexamethasone is known to inhibit the induction of iNOS, and the aim of the current study was to determine the effect of dexamethasone on viability and NOS activity in an ischemic flap model on the dorsum of the rat. Vehicle (N = 20) or dexamethasone (N = 20) was administered 3 hours prior to operation. The surviving area was measured and the flaps were removed after 24 hours for 10 rats in each group and after 48 hours for the remaining 10 rats in each group. Treatment with dexamethasone resulted in an improved flap viability at both 24 hours (p < 0.001) and 48 hours (p < 0.01), and a reduced induction of Ca2+-independent NOS activity in the proximal part of the flaps at 24 hours (p < 0.001). In the current study the authors show that dexamethasone attenuates the induction of Ca2+-independent NOS and increases survival in experimental skin flaps.

Animals↗

Short-term increase and long-term decrease of blood pressure in response to oxytocin-potentiating effect of female steroid hormones.

To investigate how the effects of oxytocin on blood pressure are influenced by female sex hormones, oxytocin (1 mg/kg, s.c.) was given to intact cycling and ovariectomized (OVX) female rats. Oxytocin caused a transient increase in blood pressure, most pronounced during proestrus (p < 0.01) and estrus (p < 0.01). This increase was partially antagonized by an oxytocin antagonist. When oxytocin was given for 5 days, blood pressure decreased (intact rats: 123+/-1.5 vs. 130+/-1.3 mm Hg; p < 0.001, OVX rats: 120+/-3.0 vs. 129+/-1.1 mm Hg; p < 0.001). This decrease, not abolished by the oxytocin antagonist, persisted for 3 weeks in intact rats and for 8 days in OVX rats. If oxytocin treatment of OVX rats continued, a nadir of 12 mm Hg (118+/-1.7 mm Hg; p < 0.001) was reached after 8 days. Thereafter heart rate decreased significantly (p < 0.05). One daily oxytocin injection for 12 days to OVX rats decreased blood pressure for 3 weeks, as in intact rats. These results show that acute and chronic oxytocin treatment cause opposite effects on blood pressure, and that these effects are modified by female sex hormones.

Analysis of Variance↗

Spinal cord stimulation improves survival in ischemic skin flaps: an experimental study of the possible mediation by calcitonin gene-related peptide.

Currently, spinal cord stimulation is used to treat ischemia and ischemic pain, with the best results observed in vasospastic cases. It was earlier demonstrated that spinal cord stimulation may attenuate experimentally induced vasospasm in an island flap in the rat. The present study was designed to investigate whether preemptive spinal cord stimulation could increase long-term flap survival and to explore the neurohumoral mediation of the effect. A total of 56 rats were implanted with chronic spinal cord stimulation systems. Three days later, a groin flap based on the superficial epigastric vessels was harvested, and the single feeding artery was occluded by a detachable microvascular clip. After 12 hours, the clip was removed. Flap survival was evaluated after 7 days. Immediately before flap surgery, two groups of animals received 30 minutes of stimulation using current clinical parameters and with stimulation amplitudes of 70 (n = 10) or 90 percent (n = 8) of that evoking muscular contractions. The outcomes in these groups were compared with those in two control groups (n = 20; n = 10). In one group, an additional calcitonin gene-receptor peptide (CGRP) antagonist was intravenously injected before stimulation (n = 8). In the control groups without stimulation, virtually all flaps necrotized. In treated groups, flap survival was 60 percent at the lower intensity and almost 90 percent at the higher one. The administration of a CGRP antagonist before treatment reduced its efficacy to below 40 percent survival. The differences between the untreated and treated groups were significant. The decrease in survival after CGRP-receptor block was significant in one of two tests. Preemptive spinal cord stimulation increases survival of skin flaps with critical ischemia. The effects are dependent on the stimulation intensity and are possibly mediated by the release of CGRP in the periphery.

Animals↗

TMJ pain in relation to circulating neuropeptide Y, serotonin, and interleukin-1 beta in rheumatoid arthritis.

AIMS: The aim of this study was to test the hypothesis that temporomandibular joint (TMJ) pain is influenced by circulating levels of neuropeptide Y, serotonin, and interleukin-1 beta in rheumatoid arthritis. METHODS: Forty-three seropositive (RF+) or seronegative (RF-) rheumatoid arthritis patients and 24 healthy individuals were included in the study. RESULTS: High serum concentrations of serotonin were associated with low TMJ pressure pain thresholds and pain during mandibular movement in the RF+ patients. The results of this study do not support a relationship between circulating neuropeptide Y or interleukin-1 beta and TMJ pain. The RF+ patients had higher C-reactive protein levels and erythrocyte sedimentation rates than the RF- patients. There were also higher plasma levels of interleukin-1 beta in the RF+ patients than in the healthy individuals. Plasma levels of neuropeptide Y in the RF- patients were higher than in the healthy individuals. CONCLUSION: This study indicates that the serum concentration of serotonin is associated with TMJ allodynia in seropositive rheumatoid arthritis.

Adult↗

Pain, allodynia, and serum serotonin level in orofacial pain of muscular origin.

AIMS: This study was conducted to investigate the serum level of serotonin (S-5-HT) in patients with temporomandibular disorders (TMD) of muscular origin, i.e., localized myalgia, and to compare it to that found in healthy individuals and patients with fibromyalgia. A second aim was to investigate the association between S-5-HT and pain parameters. METHODS: Twenty patients with localized myalgia participated in the study. Twenty age- and gender-matched healthy individuals and twenty patients with fibromyalgia served as controls. The participants were examined clinically as to the condition of the temporomandibular region and S-5-HT. RESULTS: The levels of S-5-HT did not differ significantly between the groups. However, in patients with localized myalgia there was a negative correlation between S-5-HT and tenderness of the temporomandibular muscles. CONCLUSION: The results of this study indicate that allodynia of orofacial muscles in patients with TMD is significantly related to S-5-HT concentration.

Adult↗

Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide.

OBJECTIVES: To establish whether 24 h urinary excretion of the potent vasodilator calcitonin gene-related peptide (CGRP) was higher in postmenopausal women with vasomotor symptoms compared to the level in women without symptoms. We also wanted to establish whether urinary excretion of CGRP changed during the menstrual cycle in women of fertile age. MATERIAL AND METHODS: Thirteen postmenopausal women with and 13 women without vasomotor symptoms were included. Urine was collected over 24 h and CGRP excretion was measured utilizing radio-immunoassay technique. Twenty-four hour CGRP excretion was also measured in ten fertile women with regular cycles in early follicular, preovulatory and midluteal phase. RESULTS: Twenty-four hour urinary excretion of CGRP was significantly higher in women with vasomotor symptoms compared to non-flushing women (median 7.16 vs 5.15 pmol/24 h; P = 0.028). CGRP concentrations were stable throughout the ovulatory cycles. CONCLUSION: The 24 h urinary excretion of CGRP is higher in women with vasomotor symptoms than in women without these symptoms. CGRP may be the mediator of vasodilator signals originating from the thermoregulatory center.

Calcitonin Gene-Related Peptide↗

Activation of vagal afferents after intravenous injection of interleukin-1beta: role of endogenous prostaglandins.

Intravenous administration of interleukin-1 (IL-1) activates central autonomic neuronal circuitries originating in the nucleus of the solitary tract (NTS). The mechanism(s) by which blood-borne IL-1 regulates brain functions, whether by operating across the blood-brain barrier and/or by activating peripheral sensory afferents, remains to be characterized. It has been proposed that vagal afferents originating in the periphery may monitor circulating IL-1 levels, because neurons within the NTS are primary recipients of sensory information from the vagus nerve and also exhibit exquisite sensitivity to blood-borne IL-1. In this study, we present evidence that viscerosensory afferents of the vagus nerve respond to intravenously administered IL-1beta. Specific labeling for mRNAs encoding the type 1 IL-1 receptor and the EP3 subtype of the prostaglandin E2 receptor was detected in situ over neuronal cell bodies in the rat nodose ganglion. Moreover, intravenously applied IL-1 increased the number of sensory neurons in the nodose ganglion that express the cellular activation marker c-Fos, which was matched by an increase in discharge activity of vagal afferents arising from gastric compartments. This response to IL-1 administration was attenuated in animals pretreated with the cyclooxygenase inhibitor indomethacin, suggesting partial mediation by prostaglandins. In conclusion, these results demonstrate that somata and/or fibers of sensory neurons of the vagus nerve express receptors to IL-1 and prostaglandin E2 and that circulating IL-1 stimulates vagal sensory activity via both prostaglandin-dependent and -independent mechanisms.

Acute-Phase Reaction↗

Development of systemic lupus erythematosus in mice is associated with alteration of neuropeptide concentrations in inflamed kidneys and immunoregulatory organs.

In the present study we used a well-characterised model of murine lupus, the female NZB/W hybrid, to study the possible involvement of neuropeptides in the pathogenesis of systemic lupus erythematosus (SLE). Analysis of neuropeptides with a possible role in inflammation showed that substance P (SP) calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) are present in increased quantities in the inflamed kidneys of SLE mice, confirming their involvement in local inflammation, while there is a general reduction in the peptide concentrations in the lymphoid organs of lupus mice, except for NPY. Our results suggest that the altered neuropeptide concentrations observed in the SLE lymphoid organs may be partly responsible for the altered immune response and contribute to the development of autoimmune diseases.

Animals↗

Effects of calcitonin gene-related peptide-(8-37) on withdrawal responses in rats with inflammation.

The present study was performed to explore the effect of subcutaneous injection of carrageenan into the rat plantar region on hindpaw edema formation and the latency of hindpaw withdrawal to presumed nociceptive stimulation. Subcutaneous injection of carrageenan into the left hindpaw induced a significant increase in the volume of the left hindpaw, leaving the right side unaffected. In addition, we found a bilateral decrease in hindpaw withdrawal latency to heat and mechanical, but not to cold stimulation. The decreased bilateral hindpaw withdrawal latency to heat stimulation lasted for 14 days after carrageenan injection. The decreased bilateral hindpaw withdrawal latency to mechanical stimulation lasted for 2 days after the injection, then reversed and increased from day 3 to 14. Intrathecal injection of either 10 nmol of calcitonin gene-related peptide 8-37 or 26.6 nmol of morphine induced significant bilateral increases in hindpaw withdrawal latency, which were more pronounced with the morphine. The results show that experimentally induced unilateral hindpaw inflammation induces a bilateral decrease in hindpaw withdrawal latencies to presumed nociceptive stimulation while the sensory systems for heat and mechanical stimulation were differently affected after carrageenan injection.

Analgesics, Opioid↗

[Pain analysis is vital in rheumatic diseases. The pain is often the patient's worst problem].

The article consists of a synthesis of a rheumatic pain symposium held at the annual meeting of the Swedish Medical Association in 1996. Various aspects of pain in rheumatic diseases were discussed, such as physiological, neurohumoral and neurogenic mechanisms, sensory stimulation treatment, differentiation of mechanical and inflammatory pain, quality enhancement by improved cooperation between primary and tertiary care facilities, pharmacological treatment with (centrally and peripherally acting) opioids, selective cyclo-oxygenase inhibitors, and NMDA (N-methyl-D-aspartate) receptor antagonists. The aim of the symposium, with its focus on the manifest pain problem, was to improve our knowledge and skill in the understanding and treatment of this large patient category. For patients with rheumatic disorders exacerbated by pain problems, as for other patients, a pain diagnosis is of fundamental importance. This can be achieved by analysis of the social, psychological, physiological and medical factors contributing to the cause and degree of pain and to pain behaviour, and of the extent to which the pain may be nociceptive (i.e., inflammatory, mechanical, or ischaemic in origin), neurogenic or idiopathic. Pain analysis should be followed by individualised treatment focused on the patient's most crucial problems, thus enhancing the prospect of optimal treatment outcome.

Analgesia↗

Reproducibility of manual pressure force on provocation of the sacroiliac joint.

BACKGROUND AND PURPOSE: Previous studies of pain-provocation sacroiliac (SI) joint tests have revealed conflicting results. The aim of the present study was to evaluate the intra- and inter-test reliability of pressure force applied during distraction test, compression test and pressure on the apex sacralis. METHODS: Seventeen physiotherapists (PTs), median age 43 years and median clinical experience 11 years, all experienced in musculoskeletal evaluation and therapy, participated in the study. Each PT performed each test on the same healthy volunteer for 20 s, on three separate occasions, at intervals of one week using a specially constructed examination table which registered pressure force. RESULTS: The PTs were capable of maintaining a relatively constant pressure force for 20 s. The intra-test reliability was acceptable even though there were individual differences on different occasions between those PTs who used the SI joint tests often and those who seldom or never used them. The inter-test reliability was insufficient. CONCLUSIONS: The findings indicate the advantage of registering pressure force as a complement for standardized methods for pain-provoking tests and when learning provocation tests, since individual variability was considerable.

Adult↗