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Biomedical subjects

Thomas Lundeberg

Publications and source records attributed to Thomas Lundeberg.

At least 37 records · Page 2Linked to original sources
PubMed2005

Gene expression analysis of human epidermal keratinocytes after N-acetyl L-cysteine treatment demonstrates cell cycle arrest and increased differentiation.

OBJECTIVES: Several cancer prevention programmes have previously been executed using treatment of antioxidant compounds. The antioxidant N-acetyl L-cysteine (NAC), a membrane-permeable aminothiol, is a sulfhydryl reductant reducing oxidised glutathione, as well as being a precursor of intracellular cysteine and glutathione. A previous report based on the cellular response to NAC treatment showed that NAC induced a 10-fold more rapid differentiation in normal primary keratinocytes as well as a reversion of a colon carcinoma cell line from neoplastic proliferation to apical-basolateral differentiation. In order to investigate molecular events underlying the changes in proliferation and differentiation induced by NAC treatment, we performed global gene expression analysis of normal human epidermal keratinocytes in a time series. METHODS: Treated samples were compared to untreated samples through a reference design using a spotted cDNA array comprising approximately 30,000 features. B statistics was used to identify differentially expressed genes, and RT-PCR of a selected set of genes was performed to verify differential expression. RESULTS: The number of differentially expressed genes increased over time, starting with 0 at 30 min, 73 at 3 h and increasing to 952 genes at 48 h. Results of the expression analysis showed arrest of the cell cycle and an upregulation of cytoskeletal reorganisation, implicating increased differentiation. A comparison to gene ontology groups indicated downregulation of a large number of genes involved in cell proliferation and regulation of the cell cycle. CONCLUSIONS: A significant fraction of the differentially expressed genes could be classified according to their role in the differentiation process, demonstrating that NAC regulates the conversion from proliferation to differentiation at a transcriptional level.

Acetylcysteine↗
PubMed2004

Gender differences in electrical pain threshold responses to transcutaneous electrical nerve stimulation (TENS).

Gender differences in pain perception have been frequently discussed, but the documented gender-related pain-alleviating effects of non-pharmacological methods are sparse. In this study we aimed to investigate changes in electrical sensory thresholds and electrical pain thresholds, in response to high frequency transcutaneous electrical nerve stimulation, TENS, for 20 min in healthy women (n=29) and men (n=29). The thresholds were assessed pre-, during-, and post-TENS. The pattern of change in thresholds was evaluated with a rank-based statistical method regarding the level of systematic change, expressed as relative position (RP) and additional individual changes, expressed as relative rank variance (RV), with its 95% confidence intervals. Equal levels of systematic changes towards increased electrical sensory thresholds were seen in women and men post-TENS (RP, 0.35; 95% CI, 0.07, 0.63, and RP, 0.36; 95% CI, 0.17, 0.53, respectively). At the same point of time, systematic changes towards increased electrical pain thresholds were only seen in women (RP, 0.43; 95% CI, 0.27, 0.60), while they were unchanged in men (RP, -0.01; 95% CI, -0.13, 0.10). Significant additional individual variations were found in the women's responses of assessed electrical sensory and pain thresholds but not in the men's. It is concluded that both women and men responded with a significant increase of the electrical sensory threshold to high frequency TENS, but only women responded with increase of the electrical pain thresholds. The individual variation of the responses was greater in the women than in the men.

Adult↗
PubMed2004

Effect of electro-acupuncture stimulation of different frequencies and intensities on ovarian blood flow in anaesthetized rats with steroid-induced polycystic ovaries.

BACKGROUND: Maintenance of ovarian blood flow (OBF) is suggested to be important for regular ovulation in women with polycystic ovaries (PCO). The purpose of the present study was to investigate whether electro-acupuncture (EA) of different frequencies and intensities can improve the OBF of anaesthetized rat in the animal model of PCO. METHODS: PCO was experimentally induced by a single intramuscular (i.m.) injection of estradiol valerate (EV) in rats. Control rats were given i.m. injection of oil. The involvement of the two ovarian sympathetic nerves; superior ovarian nerve (SON) and plexus ovarian nerve (OPN), in OBF responses was elucidated by severance of SON and OPN in both control and PCO rats. How systemic circulatory changes affect OBF was evaluated by continuous recording of the blood pressure. OBF was measured on the surface of the ovary-using laser Doppler flowmetry. Acupuncture needles were inserted bilaterally into the abdominal and hind limb muscles and connected to an electrical stimulator. Two frequencies--2 Hz (low) and 80 Hz (high)--with three different intensities--1.5, 3, and 6 mA--were applied for 35 s. RESULTS: Low-frequency EA at intensities of 3 and 6 mA elicited significant increases in OBF in the Control group compared to baseline. In the PCO group the increases in OBF were significant only when stimulating with low-frequency EA at 6 mA. After severance of the ovarian sympathetic nerves, the increased response of OBF that had been induced by low-frequency EA in both the Control and PCO group was abolished, indicating that the OBF response is mediated via the ovarian sympathetic nerves. High-frequency EA at 6 mA significantly decreased OBF and mean arterial blood pressure (MAP) in the Control group compared to baseline. In the PCO group, the same stimulation produced similar decreases in MAP, but not in OBF. CONCLUSION: Low-frequency EA stimulation with a strong intensity (6 mA) increases OBF in rats with steroid-induced PCO whereas less strong intensity (3 mA) induces similar changes in control rats. Severance of the ovarian sympathetic nerves, abolish this OBF increase in both study groups, which suggests that the responses of OBF to EA are mediated via the ovarian sympathetic nerves.

Anesthesia↗
PubMed2004

Substance P microinjected into the periaqueductal gray matter induces antinociception and is released following morphine administration.

The aims of the present study were to investigate, in rats, the behavioral effects of substance P (SP) microinjected into the ventrolateral periaqueductal gray (PAG) and the effects of the neurokinin 1 (NK-1) receptor antagonist [d-Arg1, d-Trp7, 9, Leu11]-substance P (Spantide). The effect of morphine administration on the release of SP in the ventrolateral PAG was also investigated using microdialysis in awake rats. SP microinjected into the ventrolateral part of the PAG induced significant increases in the hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulation as an antinociceptive response. The NK-1 receptor antagonist blocked these effects but exhibited no antinociceptive effect alone. Subcutaneous administration of morphine increased basal SP-like immunoreactivity (SP-LI) release in the microdialysate obtained from the ventrolateral PAG of freely moving rats. Our results demonstrate that SP injected into the ventrolateral PAG induces an antinociceptive effect via activation of NK-1 receptors. Morphine administered systemically induces the release of SP in the ventrolateral PAG. We suggest that an increased release of SP in the PAG may contribute to opioid antinociception.

Analgesics↗
PubMed2004

Role of corticotropin-releasing factor and its receptor in nociceptive modulation in the central nucleus of amygdala in rats.

Corticotropin-releasing factor (CRF) plays important physiological functions in the central nervous system. The present study was performed to investigate the role of CRF and CRF receptor in nociceptive modulation in the central nucleus of amygdala (CeA) of rats. The hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation increased significantly after intra-CeA administration of 0.1 and 0.01 nmol of CRF, but not 0.001 nmol, indicating that CRF induces antinociceptive effects in the CeA of rats. The antinociceptive effect may be due to the dose of CRF was attenuated by intra-CeA administration of 0.1 nmol alpha-hCRF9-41, a selective CRF receptor antagonist, suggesting that the CRF-induced antinociception is mediated by the CRF receptors in the CeA. Furthermore, the HWL to both thermal and mechanical stimulation decreased significantly after intra-CeA administration of alpha-hCRF9-41 alone, suggesting an involvement of endogenous CRF in the CeA in nociceptive modulation. The present study demonstrated that both exogenous and endogenous CRF plays an antinociceptive effect in the CeA, the effect is mediated by CRF receptor.

Afferent Pathways↗
PubMed2004

Non-pharmacological pain-relieving therapies in individuals with spinal cord injury: a patient perspective.

OBJECTIVE: To assess the non-pharmacological treatments used and preferred by patients with spinal cord injury and pain. DESIGN: A cross-sectional descriptive study. INTERVENTIONS: One hundred and twenty three patients with spinal cord injury, matched for gender, age, level of lesion and completeness of injury were assessed in 1999 at the Spinalis SCI unit, Stockholm, Sweden and followed-up in a mailed survey 3 years later. In total, 82.1% of the questionnaires (n=101) were returned. Ninety of these patients still suffered pain and were thus included in the study. MAIN OUTCOME MEASURES: Pain questionnaires, visual analogue scale (VAS), Hospital Anxiety and Depression Scale and Life Satisfaction instrument. RESULTS: 63.3% of the patients had tried non-pharmacological treatments, where acupuncture, massage and transcutaneous electrical nerve stimulation (TENS) were the most commonly tried. Predictive for having tried non-pharmacological treatment were high ratings of pain intensity, presence of aching pain, and cutting/stabbing pain. CONCLUSION: Massage, and heat were the non-pharmacological treatments reported to result in the best pain alleviation. Results from our study suggest that we need to (re)evaluate the treatments offered to patients with spinal cord injury and pain and combine non-pharmacological and pharmacological treatments.

Acupuncture Therapy↗
PubMed2004

Acupuncture treatment in patients with keratoconjunctivitis sicca: a pilot study.

AIM: To evaluate the effects of acupuncture in patients with keratoconjunctivitis sicca (KCS). MATERIAL AND METHODS: Twenty-five patients (20 women, five men) with KCS were randomly assigned to an acupuncture treatment group or a control group. The effects of acupuncture were evaluated by a questionnaire on symptoms, visual analogue scale recordings, registration of drop frequency, and dry eye tests. Ten acupuncture sessions were given. Follow-up was carried out after 2-3 weeks and again after a mean period of 8 months. RESULTS: Patients receiving acupuncture felt better at the first follow-up compared with the control group (p = 0.036). However, no statistical significance could be found concerning any change, or difference, in the total number of subjective symptoms, dosage frequency or, as indicated by the dry eye tests, tear quality, tear secretion and ocular surface disease. CONCLUSION: The results indicate that acupuncture has subjective beneficial effects in patients with KCS and could therefore be tried as a complement to ordinary treatment.

Acupuncture Points↗
PubMed2004

Muscle and brain changes of calcitonin gene-related peptide in experimentally induced unilateral rat masseter myositis.

AIMS: To investigate changes in calcitonin gene-related peptide (CGRP)-like immunoreactivity (CGRP-LI) in the rat masseter muscle and brain after the unilateral experimental induction of masseter myositis. METHODS: Ipsilateral and contralateral changes of the CGRP were examined in rat masseter muscle after the induction of unilateral myositis on the right side with an intramuscular injection of 0.01 mL Freund's adjuvant. The left masseter, and left and right masseters of control rats, were injected with 0.01 mL saline (0.9%). After 21 days, tissue samples from the masseter muscles and the hypothalamic-pituitary-adrenal (HPA) axis were analyzed for the presence of CGRP by immunohistochemistry, radioactive immunoassay, and high performance liquid chromatography. Hematoxylin-eosin staining was used to confirm inflammation in the masseter muscles. RESULTS: Elevated CGRP-LI was detected bilaterally in the masseter muscles (P < .001) in the myositis group. CGRP-immunoreactive nerve fibers were mainly detected in close proximity to muscle cells and in the walls of the blood vessels. Compared to the control rats, a significant difference in scratching behavior was seen in the myositis group from day 9 until day 21. In the myositis group, CGRP-LI was increased in the pituitary gland concomitant with the increase in CGRP-LI in the masseter muscles but was decreased in the hypothalamus. A possible explanation for these changes could be that rats with chronic myositis develop an abnormal function of the HPA axis triggered by masseter muscle inflammation. CONCLUSION: The results of this study demonstrate that CGRP may play an important role both peripherally and centrally in masseter muscle myositis in association with presumed nociceptive behavior.

Animals↗
PubMed2003

Antinociceptive role of oxytocin in the nucleus raphe magnus of rats, an involvement of mu-opioid receptor.

Recent studies showed that oxytocin plays an important role in nociceptive modulation in the central nervous system. The present study was undertaken to investigate the role of oxytocin in antinociception in the nucleus raphe magnus (NRM) of rats and the possible interaction between oxytocin and the opioid systems. Intra-NRM injection of oxytocin induced dose-dependent increases in hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulation in rats. The antinociceptive effect of oxytocin was significantly attenuated by subsequent intra-NRM injection of the oxytocin antagonist 1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin. Intra-NRM injection of naloxone dose-dependently antagonized the increased HWLs induced by preceding intra-NRM injection of oxytocin, indicating an involvement of opioid receptors in oxytocin-induced antinociception in the NRM of rats. Furthermore, the antinociceptive effect of oxytocin was dose-dependently attenuated by subsequent intra-NRM injection of the mu-opioid antagonist beta-funaltrexamine (beta-FNA), but not by the kappa-opioid antagonist nor-binaltorphimine (nor-BNI) or the delta-opioid antagonist naltrindole. The results demonstrated that oxytocin plays an antinociceptive role in the NRM of rats through activating the oxytocin receptor. Moreover, mu-opioid receptors, not kappa and delta receptors, are involved in the oxytocin-induced antinociception in the NRM of rats.

Analgesics↗
PubMed2003

Involvement of calcitonin gene-related peptide and its receptor in anti-nociception in the periaqueductal grey of rats.

The present study investigated the role of calcitonin gene-related peptide (CGRP) in the modulation of nociception in periaqueductal grey (PAG) of rats. Hindpaw withdrawal latencies (HWLs) were tested by hot-plate and Randall Selitto tests. The HWLs to thermal and mechanical stimulation increased significantly after intra-PAG administration of 0.26 or 0.13 nmol of CGRP, but not 0.026 nmol of CGRP. The anti-nociceptive effects induced by CGRP were significantly blocked by intra-PAG administration of 0.026 or 0.26 nmol of the CGRP1 receptor antagonist CGRP8-37. Furthermore, administration of CGRP into the decussation of superior cerebellar peduncle, out of PAG, did not elicit anti-nociceptive effects during 60 min after the injection. The results demonstrated that CGRP plays an important role in anti-nociception in PAG of rats, and CGRP1 receptor is involved in the CGRP-induced anti-nociception.

Afferent Pathways↗
PubMed2003

Involvement of oxytocin in spinal antinociception in rats with inflammation.

The present study was conducted on rats with inflammation induced by subcutaneous injection of carrageenan into the left hindpaw. Intrathecal administration of oxytocin produced dose-dependent increases in the hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats with inflammation. The antinociceptive effect of oxytocin was blocked by intrathecal administration of atosiban, a selective oxytocin antagonist, indicating that oxytocin receptor mediates oxytocin-induced antinociception in the spinal cord. The oxytocin-induced antinociceptive effect was attenuated by intrathecal administration of the opioid antagonist naloxone, suggesting an involvement of the endogenous opioid system in oxytocin-induced antinociception in the spinal cord of rats with inflammation. Furthermore, the antinociceptive effect of oxytocin was attenuated by intrathecal injections of the mu-receptor antagonist beta-funaltrexamine and the kappa-receptor antagonist nor-binaltorphimine, but not by the delta-receptor antagonist naltrindole, illustrating that mu- and kappa-receptors, but not delta-receptor, are involved in oxytocin-induced antinociception in the spinal cord of rats with inflammation. Moreover, intrathecal administration of atosiban alone induced a hyperalgesia in rats with inflammation, indicating that endogenous oxytocin is involved in the transmission and regulation of nociceptive information in the spinal cord of rats with inflammation. The present study showed that both exogenous and endogenous oxytocin displayed antinociception in the spinal cord in rats with inflammation, and mu- and kappa-receptors were involved in oxytocin-induced antinociception.

Analgesics↗
PubMed2003

Effects of acupuncture on skin and muscle blood flow in healthy subjects.

In 14 healthy female subjects, the effects of needle stimulation (acupuncture) on skin and muscle blood flow were investigated using a non-invasive custom-designed probe and photoplethysmography (PPG). In randomised order, 2-7 days apart, three modes of needle stimulation were performed on the anterior aspect of the tibia: superficial insertion (SF), insertion into the anterior tibial muscle (Mu), and insertion into the muscle including manipulation of the needle in order to elicit a distinct sensation of distension, heaviness or numbness (DeQi). Before intervention, the subjects rested for 30 min. After the intervention, the needle was left in situ for 20 min. Blood flow recordings were performed intermittently from 10 min prior to the intervention to the end of the trial. In a fourth session, serving as control, corresponding measurements were performed without any needle stimulation. Area under curve was calculated for 5-min periods prior to and after stimulation, respectively, and for the remaining 15-min period after stimulation. Compared to the control situation, muscle blood flow increased following both Mu and DeQi for 20 min, with the latter being more pronounced for the initial 5 min. Skin blood flow increased for 5 min following DeQi. However, no increase was found following SF. The DeQi stimulation was preceded by higher visual analogue scale ratings of anxiety prior to stimulation, which might have influenced skin blood flow to some extent. The results indicate that the intensity of the needling is of importance, the DeQi stimulation resulting in the most pronounced increase in both skin and muscle blood flow.

Acupuncture Points↗
PubMed2003

Steroid-induced polycystic ovaries in rats: effect of electro-acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF), and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system.

Previous studies on the effect of repeated electro-acupuncture (EA) treatments in rats with steriod-induced polycystic ovaries (PCO), EA has been shown to modulate nerve growth factor (NGF) concentration in the ovaries as well as corticotropin releasing factor (CRF) in the median eminence (ME). In the present study we tested the hypothesis that repeated EA treatments modulates sympathetic nerve activity in rats with PCO. This was done by analysing endothelin-1 (ET-1), a potent vasoconstrictor involved in ovarian functions, as well as NGF and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. The main result in the present study was that concentrations of ET-1 in the ovaries were significantly lower in the PCO group receiving EA compared with the healthy control group (p < 0.05). In the hypothalamus, however, ET-1 concentrations were found to be significantly higher in the PCO group receiving EA than in the healthy control group (p < 0.05). Concentrations of ovarian NGF protein were significantly higher in the PCO control group compared with the healthy control group (p < 0.001), and these concentrations decreased significantly after repeated EA treatments compared with those in the PCO control group (p < 0.05) and were found to be the same as those in the healthy control group. In conclusion, these results indicate that EA modulates the neuroendocrinological state of the ovaries, most likely by modulating the sympathetic nerve activity in the ovaries, which may be a factor in the maintenance of steroid-induced PCO.

Adrenal Glands↗
PubMed2003

Effects on muscle pain by intramuscular injection of granisetron in patients with fibromyalgia.

We have previously reported that the level of 5-HT in the masseter muscle is increased in patients with fibromyalgia as compared with healthy subjects and that high intramuscular level of 5-HT is associated with muscle pain. We have also reported that injection of the 5-HT(3) receptor antagonist granisetron (GRA) into the masseter muscle of healthy subjects reduced pain induced by 5-HT and abolished allodynia/hyperalgesia. The aim of this study was to investigate whether GRA can influence pain and allodynia/hyperalgesia of the masseter muscle in patients with fibromyalgia. Eighteen female patients who met the criteria of fibromyalgia according to the American College of Rheumatology participated in the study. They were examined regarding pain intensity and pressure pain threshold (PPT) over the masseter muscle. One milliliter of GRA (1 mg/ml) was injected into the masseter muscle on one side and 1 ml of isotonic saline on the other side in a randomized and double-blind manner. After the injections, the pain intensity and PPT were recorded during 30 min. The pain intensity increased after injection of saline and to a lower degree after injection of GRA. The PPT increased after injection of GRA, while no such change was observed after saline. The difference between GRA and saline was, however, not significant. Eight of the patients responded to the GRA injection by an increase of PPT during the experimental period that differed from saline. They also showed a tendency to a lower increase of pain intensity after injection of GRA when compared to saline. In conclusion, the results of this study do not prove that injection of the 5-HT(3)-antagonist GRA into the masseter muscle influences local pain and allodynia/hyperalgesia in patients with fibromyalgia.

Adult↗
PubMed2003

Involvement of endogenous beta-endorphin in antinociception in the arcuate nucleus of hypothalamus in rats with inflammation.

Although exogenous administration of beta-endorphin to the arcuate nucleus of hypothalamus (ARC) had been shown to produce antinociception, the role of endogenous beta-endorphin of the ARC in nociceptive processing has not been studied directly. The aim of the present study was to investigate the effect of endogenous beta-endorphin in the ARC on nociception in rats with carrageenan-induced inflammation. The hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation was assessed by the hot-plate test and the Randall Selitto Test. Intra-ARC injection of naloxone had no significant influence on the HWL to thermal and mechanical stimulation in intact rats. The HWL decreased significantly after intra-ARC injection of 1 or 10 microg of naloxone in rats with inflammation, but not with 0.1 microg of naloxone. Furthermore, intra-ARC administration of the selective mu-opioid receptor antagonist beta-funaltrexamine (beta-FNA) decreased the nociceptive response latencies to both stimulation in a dose-dependent manner in rats with inflammation, while intra-ARC administration of the selective delta-opioid receptor antagonist naltrindole or the selective kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) showed no influences on the nociceptive response latency. The antiserum against beta-endorphin, administered to the ARC, also dose-dependently reduced the HWL in rats with inflammation. The results indicate that endogenous beta-endorphin in the ARC plays an important role in the endogenous antinociceptive system in rats with inflammation, and that its effect is predominantly mediated by the mu-opioid receptor.

Analgesics↗
PubMed2003

An antinociceptive role of galanin in the arcuate nucleus of hypothalamus in intact rats and rats with inflammation.

In the arcuate nucleus of hypothalamus (ARC), galaninergic fibers form synaptic contacts with proopiomelanocortin neurons, which are involved in pain modulation. The present study assessed the role of exogenous and endogenous galanin in the modulation of nociception in the ARC of rats. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation was assessed by the hot-plate test and the Randall Selitto Test. Intra-ARC injection of galanin dose-dependently increased the HWLs in intact rats, indicating an antinociceptive role of exogenous galanin in the ARC. The antinociceptive effect of galanin was blocked by following intra-ARC injection of galantide, a putative galanin receptor antagonist, suggesting that the antinociceptive effect of galanin is mediated by galanin receptors. Moreover, intra-ARC injection of galanin increased the HWL in rats with inflammation. Intra-ARC administration of galantide alone reduced the HWLs in rats with inflammation, while there were no influences of galantide on the HWL in intact rats. Taken together, the results show that galanin has an antinociceptive role in the ARC of intact rats and rats with inflammation.

Animals↗
PubMed2003

Neuronal plasticity in relation to nociception and healing of rat achilles tendon.

Nerve regeneration and the occurrence of three neuropeptides; i.e. substance P (SP), calcitonin gene related peptide (CGRP) and galanin (GAL), were studied during healing of tendon rupture in the rat by semi-quantitative immunohistochemistry. The neuronal findings were related to nociception as assessed by hindpaw withdrawal latencies at thermal and mechanical tests. Experimental rupture of rat Achilles tendon--normally devoid of nerves--elicited extensive nerve ingrowth into the rupture site in the early phase of healing followed by almost complete fiber disappearance (weeks 12-16). The ingrowth of SP and CGRP positive fibers, seen already at weeks 1-2, was associated with increased nociception. Subsequently, the occurrence of GAL positive fibers at weeks 4-6 was associated with decreased nociception. An even stronger relationship to nociception during healing was observed when the rate of change in neuropeptide expression instead of the expression in absolute terms was considered, according to the "cascade" formula of SP(')+CGRP(')-GAL(').It may prove that the observed temporal occurrence of different neuropeptides reflects a role of the peripheral nervous system in regulating synchronously nociception and healing.

Achilles Tendon↗