Biomedical subjects

T Lundeberg

Publications and source records attributed to T Lundeberg.

At least 19 recordsLinked to original sources

PubMed1999

Intra-periaqueductal grey injection of galanin increases the nociceptive response latency in rats, an effect reversed by naloxone.

The nociceptive response latencies were increased significantly after intra-periaqueductal grey (PAG) administration of 1.0 or 3.0 nmol of galanin, but not 0.3 nmol, in rats. The effect of galanin was attenuated by following injection of 5.5 nmol of naloxone into PAG. These results indicate an anti-nociceptive role of galanin, and a possible interaction between galanin and opioid peptides in PAG in rats.

Animals↗

PubMed1999

Cholecystokinin-8 protects central cholinergic neurons against fimbria-fornix lesion through the up-regulation of nerve growth factor synthesis.

In this study, we demonstrate that cholecystokinin-8 (CCK-8) induces an increase in both nerve growth factor (NGF) protein and NGF mRNA in mouse cortex and hippocampus when i.p. injected at physiological doses. By using fimbria-fornix-lesioned mice, we have also demonstrated that repeated CCK-8 i.p. injections result in recovery of lesion-induced NGF deficit in septum and restore the baseline NGF levels in hippocampus and cortex. Parallel to the effects on NGF, CCK-8 increases choline acetyltransferase (Chat) activity in forebrain when injected in unlesioned mice and counteract the septo-hippocampal Chat alterations in fimbria-fornix-lesioned mice. To assess the NGF involvement in the mechanism by which CCK-8 induces brain Chat, NGF antibody was administrated intracerebrally to saline- and CCK-8-injected mice. We observe that pretreatment with NGF antibody causes a marked reduction of NGF and Chat activity in septum and hippocampus of both saline- and CCK-8-injected mice. This evidence indicates that the CCK-8 effects on cholinergic cells are mediated through the synthesis and release of NGF. Taken together, our results suggest that peripheral administration of CCK-8 may represent a potential experimental model for investigating the effects of endogenous NGF up-regulation on diseases associated with altered brain cholinergic functions.

Animals↗

PubMed1999

Response of the gastric vagal afferent activity to cholecystokinin in rats lacking type A cholecystokinin receptors.

A systemic administration of cholecystokinin (CCK) increases gastric vagal afferent activity via type A CCK receptors (CCKAR). In the present study, the response of gastric vagal afferent activity to an intravenous administration of CCK was investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which lack CCKAR, and compared with its control strain, Long-Evans Tokushima Otsuka (LETO) rats. The intravenous administration of 300 pmol kg(-1) and 3 nmol kg(-1) of CCK elicited dose-dependent increases in the gastric vagal afferent activity in LETO rats. The responses were not influenced by the pretreatment with L-365,260, a type B CCK receptor (CCKBR) antagonist, while they were significantly diminished by pretreatment with MK-329, a CCKAR antagonist. After pretreatment with MK-329, 3 nmol kg(-1) (but not 300 pmol kg(-1)) of CCK still elicited a small but significant increase in the activity. In the OLETF rats, both 300 pmol kg(-1) and 3 nmol kg(-1) of CCK produced small increases in the vagal afferent activity, and the responses were not influenced by pretreatment with either L-365,260 or MK-329. In addition, the systemic administration of CCK did not change gastric motility in the OLETF rats, indicating that the response of the vagal afferent activity in OLETF rats was independent of the gastric motility change. These results demonstrate that neither CCKAR nor CCKBR contributes to the response of the afferent activity of the gastric vagal nerve to a systemic administration of CCK in OLETF rats, suggesting an involvement of novel (non-A, non-B) CCK receptors.

Animals↗

PubMed1999

Prognostic value of the pilocarpine test to identify patients who may obtain long-term relief from xerostomia by acupuncture treatment.

BACKGROUND: Xerostomia (dry mouth) is a clinical symptom due to a number of factors, including Sjögren syndrome and radiation treatment to the head and neck region. It has been reported that acupuncture increases the salivary flow rate (SFR) in healthy subjects and in patients with xerostomia. A prognostic tool that would allow the care provider to identify patients who may respond to acupuncture treatment will aid in early intervention and thus lead to normalized SFR or relief of symptoms. OBJECTIVES: To determine the prognostic value of a test using pilocarpine chloride to identify those patients with xerostomia who may achieve a long-term increase in SFR in response to acupuncture. DESIGN: Cohort clinical study of 10 months' duration. SETTING: School of dentistry in a large, urban, research institute. PATIENTS: Thirty-two consecutive patients with xerostomia due to radiation treatment (n = 21) or Sjögren syndrome (n=11). INTERVENTION: Salivary flow rates for unstimulated whole saliva and paraffin-chewing stimulated whole saliva were measured before and after the administration of individualized doses of pilocarpine. All patients were then given 24 acupuncture treatments and followed up at 1 and 6 months. The effects of acupuncture treatment on SFR were recorded and response compared with the results of the pilocarpine test. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive value of the pilocarpine test based on changes in SFR, defined as a 20% increase or greater, following acupuncture treatment, compared with response to the pilocarpine test. RESULTS: At the 1-month follow-up, 18 (72%) of 25 patients with a positive pilocarpine test result had defined significant changes in SFR; 4 (67%) of 6 patients with a negative pilocarpine test result had an unchanged SFR. At this point, the sensitivity of the pilocarpine test was 0.90 (95% confidence interval [CI], 0.68-0.99) and the specificity was 0.36 (95% CI, 0.11-0.69). The positive predictive value was 0.72 (95% CI, 0.51-0.88), and the negative predictive value was 0.67 (95% CI, 0.22-0.96). At the 6-month follow-up, 17 (74%) of 23 patients with a positive pilocarpine test result had defined significant changes in SFR; 3 (60%) of 5 patients with a negative pilocarpine test result had an unchanged SFR. At this point, the sensitivity of the pilocarpine test was 0.89 (95% CI, 0.67-0.99), and the specificity was 0.33 (95% CI, 0.07-0.70). The positive predictive value was 0.74 (95% CI, 0.52-0.90), and the negative predictive value was 0.60 (95% CI, 0.15-0.95). CONCLUSION: The pilocarpine test was found to have a high sensitivity and good positive predictive value in identifying patients who may respond to acupuncture for the treatment of xerostomia.

Acupuncture Therapy↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

[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↗

PubMed1998

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↗