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PubMed2001

Effects of age on temporal summation and habituation of thermal pain: clinical relevance in healthy older and younger adults.

Although the effects of aging on the experience of clinical pain seem relatively clear, investigations of age-related changes in pain perception using laboratory-based pain assessment procedures have yielded contradictory findings. One potential source of variability in this literature is the type of experimental noxious stimulus that is used. Although thermal pain thresholds are the most commonly reported measure of pain sensitivity, use of suprathreshold stimuli in pain assessment procedures may yield additional, more clinically relevant information concerning the effects of aging on the experience of pain. The present study examined the effects of age on temporal summation of both the intensity and unpleasantness of thermal pain at multiple stimulus temperatures. Specifically, responses to repetitive thermal stimuli delivered to the volar forearm at 47 degrees C, 50 degrees C, and 53 degrees C were assessed in 34 younger (mean age, 22.4 years) and 34 older (mean age, 62.2 years) healthy volunteers. Results suggested that for the 47 degrees C and 50 degrees C stimulus trains, older adults exhibited higher ratings of the intensity and unpleasantness of thermal pain and enhanced temporal summation of thermal pain relative to younger adults. Moreover, thermal pain sensitivity was inversely related to perceptions of general health and to reports of recent clinical pain among younger, but not older, subjects. Collectively these findings may indicate small, although potentially significant, age-related alterations in the plasticity of the central nervous system or endogenous pain-modulatory capacities.

Journal Article↗

PubMed1997

Beta-endorphin in the brain. A role in nociception.

We have known the endogenous opioid peptide beta-endorphin for 20 years. Surprisingly, our knowledge of the physiological role of this peptide and its receptors in modulation of pain perception is still fragmentary. Whereas most studies have tried to elucidate the physiological role of beta-endorphin by reversing evoked responses by the opioid antagonist naloxone, this review focuses on quantification of release of beta-endorphin in the brain as the approach to define physiological and pathophysiological roles of beta-endorphin in relation to nociception. Using a lateral ventricle-cisterna magna perfusion model in the anesthetized rat, it was shown that depolarization of neurons in the arcuate nucleus of the hypothalamus, where beta-endorphin in produced, was followed by release of beta-endorphin to the cerebrospinal fluid compartment. Intense activation of spinal nociceptive pathways by intrathecal capsaicin injections also led to beta-endorphin release. It is concluded that there may still be good reason to quantify beta-endorphin in human cerebrospinal fluid to elucidate the role of beta-endorphin in pain perception.

Animals↗

PubMed2006

Analgesic efficacy of the cyclooxygenase-inhibiting nitric oxide donor AZD3582 in postoperative dental pain: Comparison with naproxen and rofecoxib in two randomized, double-blind, placebo-controlled studies.

OBJECTIVE: This study assessed the analgesic efficacy of single doses of 4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate (AZD3582) in acute postoperative dental pain after the removal of an impacted mandibular third molar (ie, wisdom tooth). METHODS: Two randomized, placebo-controlled, double-blind studies were performed. In a dose-finding study, 242 patients were randomized to AZD3582 375, 750, 1500, or 2250 mg (n = 41, 37, 42, and 41, respectively); naproxen 500 mg (n = 39); or placebo (n = 42). In a comparator study, 282 patients were randomized to AZD3582 500 mg (n = 78) or 750 mg (n = 83), rofecoxib 50 mg (n = 80), or placebo (n = 41). Primary outcomes included time to rescue medication, time to pain relief, and mean pain intensity difference (MPID), as well as safety profile. Pain was rated on a visual analog scale. RESULTS: In the dose-finding study, 52% (126/242) were women; the mean (SD) age was 25.1 (4) years, mean weight was 69.0 kg, and the mean (SD) body mass index (BMI) was 23.7 (3) kg/m2. In the comparator study, 58% (164/282) were women; the mean (SD) age was 27 (6.4) years, mean weight was 71 kg, and mean (SD) BMI was 24.2 (3) kg/m2. In the dose-finding study, the AZD3582 750-, 1500-, and 2250-mg groups were superior to placebo in the primary variables "time to rescue medication (0-8 hours)" (hazard ratios [HRs] [95% CIs], 0.17 [0.07-0.42], P < 0.003; 0.23 [0.11-0.50], P < 0.001; and 0.15 [0.06-0.36], P < 0.001, respectively), "time to meaningful pain relief" (HRs [95% CIs], 3.42 [1.87-6.25], P < 0.003; 2.49 [1.37-4.50], P < 0.003; and 3.07 [1.70-5.55], P < 0.001, respectively), and MPID (analysis of covariance [ANCOVA] least squares mean [LSM] differences [95% CIs], 25.8 [17.3-34.4], P < 0.003; 20.4 [12.1-28.7], P < 0.003; and 29.3 [20.9-37.6], P < 0.001, respectively). AZD3582 and naproxen did not show any statistically significant differences for the 3 primary variables, except that naproxen was superior to the AZD3582 375-mg dose for the variables time to meaningful pain relief (HR difference, 0.48 [95% CI, 0.29-0.78], P < 0.004) and MPID (difference in ANCOVA LSM, -10.2, [95% CI, -18.2 to -2.2], P < 0.012). The median times to meaningful pain relief were 115 minutes for AZD3582 375 mg, 66 minutes for 750 mg, 85 minutes for 1500 mg, 81 minutes for 2250 mg, and 162 minutes for placebo (P = NS, P = 0.003, P < 0.003, and P < 0.001, respectively). The median time to first rescue medication was 144 minutes for placebo, and <50% of the subjects on any of the AZD3582 doses or naproxen took rescue medication within 8 hours after dosing. In the comparator study, AZD3582 750 mg was superior to placebo in "time to rescue medication (0-24 hours)" (HR [95% CI], 0.4 [0.3-0.6], P < 0.001), "time to confirmed perceptible pain relief" (2.1 [1.1-3.8], P = 0.02), and MPID (11.9 [4.2-19.5], P = 0.002). However, inferiority of AZD3582 to rofecoxib for MPID could not be excluded (tolerance limit of 10 mm; P = NS for noninferiority testing). The median times to confirmed perceptible pain relief were 45 minutes for AZD3582 500 mg, 40 minutes for 750 mg, and 37 minutes for rofecoxib. The median times to first rescue medication were 218 minutes for AZD3582 500 mg, 365 minutes for 750 mg, 635 minutes for rofecoxib, and 90 minutes for placebo. Overall, AZD3582 was well tolerated. However, an effect on orthostatic blood pressure could not be excluded because there seemed to be more subjects with dizziness and orthostatic blood pressure reduction who were administered AZD3582 > or =750 mg. The proportions of patients with vertigo and decreased orthostatic blood pressure each group were as follows: AZD3582 500 mg, 6%; AZD3582 750 mg, 12%; rofecoxib, 3%; and placebo, 5%. CONCLUSIONS: AZD3582 750 mg had similar analgesic efficacy as equimolar doses of naproxen, but noninferiority to rofecoxib was not demonstrated.

Adolescent↗

PubMed1988

Arterial hypertension is associated with hypalgesia in humans.

An association between increased blood pressure and hypalgesia has been reported in several studies in animals and in a few reports in humans. We investigated the relationship between hypertension and pain perception by comparing the response to graded electrical stimulation of the tooth pulp, which is thought to represent an exclusively nociceptive system. The test was performed with a commercial tooth pulp tester in a large series of subjects with borderline or established hypertension and in three groups of normotensive controls: volunteers, nonhypertensive patients, and medical students with a well-established or no family history of hypertension. Subjects had to report when they started to feel pulp stimulation (sensory threshold) and when this became painful (pain threshold). Sensory and pain thresholds were obtained as means of the measurements on four healthy, unfilled teeth. Sensory thresholds were significantly higher in subjects with borderline or established hypertension than in two of the three normotensive groups (volunteers and normotensive patients), whereas no significant difference was observed between the two hypertensive groups. The results for the pain threshold were qualitatively similar but less clear and less amenable to statistical analysis because this parameter could not be determined with accuracy in a number of subjects in whom the subjective pain threshold was above the upper range of stimulation of the instrument. The association between blood pressure levels and pain perception was further confirmed by the highly significant correlation found for the overall data between mean arterial blood pressure and both thresholds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2001

Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel.

Calcium influx through N-type calcium channels mediates synaptic transmission at numerous central synapses and transduces nociceptive information in the spinal dorsal horn. However, the precise role of N-type calcium channels in pain perception is not fully elucidated. To address this issue, we generated and analyzed knockout mice for alpha(1B,) the pore-forming subunit of the N-type calcium channel. Homozygous mutants are viable, fertile, and show normal motor coordination. In small-diameter dorsal root ganglion neurons from mutants the density of calcium channel currents is significantly reduced, which can be accounted for by the abolition of N-type currents. We performed several pain-related behavioral tests using the mutant mice. alpha(1B)-Deficient mice show reduced response to mechanical stimuli in the von Frey test and increased tail flick latency in response to radiant heat, indicating altered spinal reflexes. However, pain response in the hot plate test is normal. In the formalin paw test, the mutant mice exhibit significantly attenuated response in Phase 2, but normal pain behaviors in Phase 1. The response to visceral inflammatory pain caused by acetic acid is also reduced in alpha(1B) knockout mice. These results suggest that the alpha(1B) subunit of N-type calcium channel plays a major role in pain perception by acting at the spinal level, but not at the supraspinal level.

Animals↗

PubMed1995

[Stellate ganglion block with transcutaneous electric nerve stimulation (TENS): a double-blind study with healthy probands].

OBJECTIVE: Blockade of the stellate ganglion is an established and highly effective diagnostic and therapeutic procedure for management of certain acute and chronic pain syndromes or other disorders. The paratracheal injection of a local anaesthetic is the simplest and most frequently used approach for blocking the cervicothoracic sympathetic nerves (ganglion stellate). However, since serious complications can occur during or following the anterior paratracheal technique including accidental intravenous or intraarterial injection, non-invasive methods for blockade of the stellate ganglion have been suggested. In 1980 Jenkner (15) reported the successful interruption of the sympathetic outflow from the stellate ganglion together with the relief of pain by transcutaneous electrical nerve stimulation (TENS), followed by the development of an "optimal wave form" in 1981 (14). Since we were unable to reproduce Jenkner's results of sympathetic blockade in our patients, this study was designed to investigate the effects of TENS on the sympathetic activity of the stellate ganglion in healthy volunteers. METHODS: 50 healthy volunteers were randomised into two groups (n = 25). In group I the left stellate ganglion was stimulated for 20 min by the mode described by Jenkner (monophasic pulse, small anode, large cathode, frequency 20 Hz), while group II was stimulated by conventional TENS (biphasic pulse, electrodes of identical size, frequency 100 Hz). The method of stimulation was blinded to both the investigator and the subjects investigated. Measurements included cutaneous blood flow of the volar forearm (laser Doppler), skin temperature on two sites of the cheeks (thermistor), pupil diameter and size of the palpebral fissures, sweat production (ninhydrine test) and global sensitivity and pain perception thresholds on both sides (electrical stimulation). Measurements were performed before TENS of the stellate ganglion, after 5, 10, 15 and 20 min of stimulation and 10 min after termination of TENS. Statistical analysis of the obtained data was performed by Friedman-Test and by Mann-Whitney-U-Test. p < 0.05 was assigned statistical significance. MAIN RESULTS: Skin temperature increased in both groups and on both sides by 1.2 degrees C, while skin perfusion rate, pupil size, size of the palpebral fissure and sweat production remained unchanged. Global sensitivity and pain perception thresholds of forehead decreased in both groups and on both sides, while there was no change of both parameters on the hands. CONCLUSION: No signs and symptoms of sympathetic blockade could be demonstrated in any of the groups, neither by TENS of the stellate ganglion as described by Jenkner nor by unspecific TENS. Thus, pain relief by TENS of the stellate ganglion as reported in the literature must involve other mechanisms than sympathetic blockade. In addition, TENS may not replace traditional blockade of the stellate ganglion by local anesthetics, if sympathetic blockade is required for diagnostic and therapeutic purposes.

Adult↗

PubMed1995

Evaluation of a community arthritis program in Australia: dissemination of a developed program.

OBJECTIVE: To evaluate the effectiveness of a community-based arthritis education program conducted in a number of locations throughout the Sydney, Australia, metropolitan area. METHODS: The program, based on earlier work, comprised 6 weekly sessions of 2.5 hours' duration. The study sample included 175 men and women with different types of arthritis, divided into intervention (n = 104) and control (n = 71) groups. Five outcome measures were selected to evaluate effectiveness of the program: pain perception, knowledge level, self-efficacy, disability index, and self-management behavior. RESULTS: The results indicated that the program was effective in increasing knowledge level (F[1,222] = 10.3, P = 0.001 at 6 weeks; F[1,108] = 7.8, P = 0.006 at 6 months), and a statistically significant difference was found in disability satisfaction 6 months after intervention (F[1,98] = 5.9, P = 0.01], but no statistically significant difference was found in pain perception, self-efficacy, and disability index. CONCLUSION: This research supports some of the successful outcomes which follow an arthritis education program: increased knowledge level and increased disability satisfaction.

Aged↗

PubMed2006

[Functional outcome after corrective osteotomy of the distal radius].

BACKGROUND: Malunited fractures of the distal radius frequently show disabling and painful reductions in active range of motion (AROM) of the wrist and forearm with reduced grip strength. Shortening and three-dimensional torsion of the distal radius occur with relative ulnar lengthening. Corrective osteotomy of the distal radius is indicated in these conditions. METHODS: We examined 24 of 30 patients after corrective osteotomy with respect to AROM, grip strength, DASH, and pain perception (visual analogue scale). The mean age of the population was 49 years (18-69 years), and the mean follow-up period was 22 months (6-63 months). RESULTS: Preoperative extension/flexion was 65 degrees , postoperative 92 degrees (p<0.05). Forearm rotation improved from 129 degrees preoperative to 160 degrees postoperative (p<0.01). The DASH score could be reduced from 40 (n=9) to 18 (n=24). Grip strength increased from 17 kg to 27 kg postoperative (p<0.01). Radioulnar inclination increased from 15 degrees preoperative to 24 degrees postoperative (p<0.05). Relative ulnar lengthening could be minimized from 4.3 mm to 0.7 mm (p<0.05). CONCLUSION: Data show that reconstruction of the distal radius improves grip strength and range of motion significantly with simultaneous reduction of pain perception and DASH scores.

Adolescent↗

PubMed2006

Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice.

We have previously shown that antinociceptive effects of morphine are enhanced in histamine H1 receptor gene knockout mice. In the present study, involvement of supraspinal histamine H2 receptor in antinociception by morphine was examined using histamine H2 receptor gene knockout (H2KO) mice and histamine H2 receptor antagonists. Antinociception was evaluated by assays for thermal (hot-plate, tail-flick and paw-withdrawal tests), mechanical (tail-pressure test) and chemical (formalin and capsaicin tests) stimuli. Thresholds for pain perception in H2KO mice were higher than wild-type mice. Antinociceptive effects of intracerebroventricularly administered morphine were enhanced in the H2KO mice compared to wild-type mice. Intracerebroventricular co-administration of morphine and cimetidine produced significant antinociceptive effects in the wild-type mice when compared to morphine or cimetidine alone. Furthermore, zolantidine, a selective and hydrophobic H2 receptor antagonist, enhanced the effects of morphine in all nociceptive assays examined. These results suggest that histamine exerts inhibitory effects on morphine-induced antinociception through H2 receptors at the supraspinal level. Our present and previous studies suggest that H1 and H2 receptors cooperatively function to modulate pain perception in the central nervous system.

Analysis of Variance↗

PubMed1991

[Pain and the experience of pain].

Pain research has been considerably expanded in the past few decades. Pain sensation must be differentiated from pain perception. The psychological experience of pain varies individually and depends on each patient's conditioning. Although there is an abundance of analgesics and sedatives, the patients' attitude towards pain and suffering, his or her motivation, past experiences, social environment and susceptibility towards suggestive guidance are of great importance.

Humans↗

PubMed2004

Outpatient hysteroscopic polypectomy in 237 patients: feasibility of a one-stop "see-and-treat" procedure.

STUDY OBJECTIVE: To evaluate the feasibility of a "see-and-treat" office polyp resection, using a 5-mm sheathed operative hysteroscope. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Public hospital. PATIENTS: Two hundred thirty-seven patients suffering from endometrial polyps who underwent outpatient hysteroscopy. INTERVENTIONS: Office polypectomy with anesthetic paracervical block (120 patients) or without (117 patients) using either mechanical (104 patients) or bipolar coaxial electrosurgical (107 patients) instrumentation. In 26 patients, we stopped the procedure before surgery because of intervening adverse events or polyps judged unresectable with an office-based procedure. A 10-cm visual analog scale (VAS) was used to rate patients' pelvic pain perception. MEASUREMENTS AND MAIN RESULTS: Overall effective polyp resection rate was 81.2% (191 of 235 evaluable patients). An inverse, although not significant (r = -.44) correlation was found between accomplished polypectomies and polyp size, ranging from 96.0% to 18.7% when the diameter of polyps was below 1 cm and above 4 cm, respectively (50 of 52 and 3 of 16 successfully accomplished procedures, respectively). No significant differences were found between successful resection rates (83.3% and 80.2%, respectively; p = .10) and VAS scores (2.2 +/- 2.6 and 3.6 +/- 2.9, respectively; p = .30) obtained in 79 premenopausal and 156 postmenopausal patients. Paracervical block administration (118 evaluable patients) matched with no anesthetic support (117 patients) was not associated either with an improved rate of resection (85.5% and 76.9%, respectively; p = .10) or with pelvic pain perception (VAS scores 3.3 +/- 2.9 and 3.0 +/- 2.8, respectively; p = .94). Visual analog scale scores were significantly lower (2.8 +/- 2.5 and 4.7 +/- 3.6, respectively; p = .001) and polyp resection rates were significantly higher (84.3% and 67.4%, respectively; p = .01) in 192 parous versus 43 nulliparous patients. Polypectomy failed in 44 of 235 patients (18.7%); the leading causes of failure were intolerable pelvic pain in 18 patients (7.6%) and polyp size in 17 patients (7.2%). Other than pelvic pain, the only adverse event we observed was clinical vasovagal reaction in four patients (1.7%). CONCLUSION: One-stop outpatient hysteroscopic polypectomy is effective in about 80% of patients. With proper preoperative selection, it can be offered as a reliable option to avoid general anesthesia and resectoscopic surgery.

Adult↗

PubMed2006

Differential effects of endogenous cysteine analogs on peripheral thermal nociception in intact rats.

Previous in vivo studies indicate that locally injected redox-modulating agents can sensitize polymodal peripheral skin nociceptors resulting in acute changes in pain perception. Since endogenous thiol-modifying redox agents are normally present in the interstitial tissue, and could be found in higher concentration in certain conditions (e.g., tissue injury, inflammation, and ischemia), we designed this study to evaluate the peripheral nociceptive effects of locally injected endogenous-reducing cysteine analogs, L-cysteine, D-cysteine and D,L-homocysteine and endogenous-oxidizing cysteine analogs, L-cystine, D-cystine and D,L-homocystine using the acute model of thermal peripheral nociception in intact rats. We found that the reducing cysteine analogs induced potent dose- and time-dependent hyperalgesia and conversely the oxidizing cysteine analogs induced potent dose- and time-dependent analgesia. In the presence of 3betaOH, a novel neuroactive steroid and potent voltage-dependent blocker of T-type Ca2+ channels, the hyperalgesic effects of the reducing agents were diminished, whereas the analgesic effects of the oxidizing agents were enhanced strongly suggesting that the observed nociceptive effects were, at least in part, mediated via the peripheral T channels. Our findings imply that changes in the redox states of the peripheral nociceptors (favoring either reduced or oxidized forms of cysteine molecules) may function as a local intrinsic mechanism in controlling peripheral pain perception.

Animals↗

PubMed1998

Adolescents' perceptions of pain during labor.

This descriptive study systematically described the quality and intensity of adolescents' pain during the progression of labor. The Gaston-Johansson Pain-o-Meter was administered to 33 adolescents during the three labor phases (2-4 cm, 5-7 cm, and 8-10 cm) following a contraction. The most frequently selected sensory words were cramping in Phase I and pressing in Phases II and III. Miserable and killing were the most commonly chosen affective words during the three labor phases. Using the Gaston-Johansson Pain-O-Meter and the Gaston-Johansson Pain-O-Meter Visual Analogue Scale, the total pain intensity scores were highest during phase III of labor and delivery. At-test of independent samples found that quality and intensity pain scores for primiparous and multiparous adolescent participants were not significantly different during the progression of labor. The findings of the study illustrate the value of using objective measures, such as the Gaston-Johansson Pain-O-Meter and the Gaston-Johansson Pain-O-Meter Visual Analogue Scale, to assess pain during labor. The study also demonstrated that nurses can use these tools with minimal training.

Adolescent↗

PubMed2006

Chest pain: physician perceptions and decision-making in a London emergency department.

STUDY OBJECTIVE: We describe physician perceptions of decision-making for acute coronary syndromes in the emergency department (ED) and the ways in which patient characteristics influence diagnosis. METHODS: This is a qualitative analysis of semistructured interview data from physicians practicing at an ethnically diverse and lower-income London ED. All physicians working more than 3 shifts in the department during a 1-month period were approached for interview. RESULTS: Four themes emerged from the interviews: (1) physicians emphasized the medical history when diagnosing acute coronary syndrome; (2) physicians reported communication barriers as an impediment to diagnosis; (3) physicians cited both epidemiologic data and cultural beliefs when explaining presentation differences between patient groups; (4) physicians interpreted patient complaints by comparing their clinical impressions to a "classic" or "textbook" norm. CONCLUSION: In most cases, physicians relied on the clinical history when making decisions for patients with suspected acute coronary syndromes. In reaching judgments, physicians elicited features of the presentation they thought were salient, interpreted those features in light of epidemiologic knowledge and cultural beliefs, and compared their overall impression of the patient to a "classic" or "textbook" norm. At each step, physicians' perceptions about patients influenced the data gathered and the interpretation of that data. In addition, the expected features of acute coronary syndrome were thought to differ for some patient groups. These results highlight the need for further research into the role of provider beliefs in medical decision-making.

Age Factors↗

PubMed2003

Is Ross syndrome a dysautonomic disorder only? An electrophysiologic and histologic study.

OBJECTIVE: To define the involvement of peripheral nerve fibers in Ross syndrome. METHODS: Mechanical pain perception, tactile and thermal thresholds on hand, foot dorsum, thigh, median nerve orthodromic sensory conduction velocity (SCV) and motor conduction velocity (MCV), sural nerve antidromic SCV, peroneal nerve MCV, H-reflex, F-wave, median, tibial nerve somatosensory evoked potentials (SSEPs), perioral, hand CO(2) laser late (LEPs) and ultralate evoked potentials, sympathetic skin response (SSRs), cardiovascular, Minor sweat, silastic imprint, histamine, photopletysmographic and pupil pilocarpine tests, cutaneous innervation immunohistochemical techniques were studied in 3 patients with Ross syndrome. RESULTS: Quantitative sensory testing showed altered results in patients 1 and 2, and patient 3 had a slight impairment of mechanical pain perception. Nerve conduction, except for a median nerve distal reduction of sensory conduction in patient 1, F-wave and SSEP findings were normal; H-reflex was absent at rest in all patients. Hand LEPs were absent in patient 2, ultralate potentials were absent in patients 1 and 2. Skin biopsy showed a disease duration related reduction of unmyelinated and myelinated sensory fibers and a lack of unmyelinated autonomic fibers in all patients. CONCLUSIONS: Our data suggest that Ross syndrome is a degenerative disorder involving progressive sudomotor fibers, and then epidermal sensory unmyelinated and myelinated fibers.

Adult↗

PubMed1999

H(+)-gated cation channels.

H(+)-gated cation channels are members of a new family of ionic channels, which includes the epithelial Na+ channel and the FMRFamide-activated Na+ channel. ASIC, the first member of the H(+)-gated Na+ channel subfamily, is expressed in brain and dorsal root ganglion cells (DRGs). It is activated by pHe variations below pH 7. The presence of this channel throughout the brain suggests that the H+ might play an essential role as a neurotransmitter or neuromodulator. The ASIC channel is also present in dorsal root ganglion cells, as is its homolog DRASIC, which is specifically present in DRGs and absent in the brain. Since external acidification is a major factor in pain associated with inflammation, hematomas, cardiac or muscle ischemia, or cancer, these two channel proteins are potentially central players in pain perception. ASIC activates and inactivates rapidly, while DRASIC has both a fast and sustained component. Other members of this family such as MDEG1 and MDEG2 are either H(+)-gated Na+ channels by themselves (MDEG1) or modulators of H(+)-gated channels formed by ASIC and DRASIC. MDEG1 is of particular interest because the same mutations that produce selective neurodegeneration in C. elegans mechanosensitive neurons, when introduced in MDEG1, also produce neurodegeneration. MDEG2 is selectively expressed in DRGs, where it assembles with DRASIC to radically change its biophysical properties, making it similar to the native H(+)-gated channel, which is presently the best candidate for pain perception.

Acid Sensing Ion Channels↗

PubMed1999

Norditropin SimpleXx: a liquid human growth hormone formulation, a pen system and an auto-insertion device.

Patient compliance is of vital importance for the outcome of any medical therapy. Compliance is especially a problem in long-term treatment of non-life threatening diseases, such as growth retardation in children. Until recently, all human growth hormone (hGH) products required a reconstitution process. Norditropin((R)) SimpleXx(TM) is a liquid formulation of the biosynthetic hGH product Norditropin((R)), and, together with an improved NovoPen((R)) 1.5, NordiPen(TM), and an auto-insertion device, PenMate(TM)/NordiPenMate(TM), it has been developed in order to ease the injection process for patients. A randomized, open, multicentre, crossover trial compared Norditropin((R)) SimpleXx(TM)/improved NovoPen((R)) 1.5 with freeze-dried Norditropin((R)) PenSet((R))/Nordiject((R)). A total of 67 children with GH deficiency, aged 5-18 years, were treated with either Norditropin((R)) SimpleXx(TM) for 6 weeks followed by Norditropin((R)) for 6 weeks or the opposite (sequences I and II, respectively). Acceptability/convenience and pain perception were evaluated by questionnaire after each period. The function and handling of the PenMate(TM) were evaluated in a Dutch trial by 27 GH-treated children with intrauterine growth retardation, aged 4-16 years, and their parents. All children were accustomed to using the Nordiject((R)) pen. The evaluation of the PenMate(TM) was based on a questionnaire. A similar trial was conducted in England, in which the NordiPen(TM) and the NordiPenMate(TM) were evaluated by 25 GH-treated children and their parents. Norditropin((R)) SimpleXx(TM) was found to be easier to inject by 64% of the children, and 98% of the children found the system easier to use overall. There was no difference in pain perception between the two administration systems, as judged by questionnaires and visual analogue scale score. Three out of four patients preferred to continue treatment with Norditropin((R)) SimpleXx(TM). The safety profiles of the two systems were similar. In the Dutch trial, the PenMate(TM) was found to be easy and safe to handle, even for very young children (aged 4-5 years). Of patients who took a long time to get used to the injections, 73% found that the new pen would help. A total of 88% of the children would prefer to use the PenMate(TM) in the future. Positive results of the handling tests were also reported in the British trial. The use of Norditropin((R)) SimpleXx(TM) and the auto-insertion device may improve patient compliance.

Adolescent↗

PubMed2005

RANTES, MDC and SDF-1alpha, prevent the HIVgp120-induced food and water intake decrease in rats.

Human immunodeficiency virus (HIV)-wasting syndrome might be facilitated by the HIVgp120 affecting the immunological system. We studied the effect (subchronic administration: 5 days) of HIVgp120, and a few immune-response mediators: regulated upon activation normal T-cell expressed and presumably secreted (RANTES), stromal derived factor-1alpha (SDF-1alpha), macrophage-derived chemokine (MDC), and their combination, on food and water intake in rats, motor control and pain perception. Eighty male adult Wistar rats received an intracerebroventricular (icv) administration of: vehicle 5 microl/day or 0.92 nmol daily of HIVgp120IIIB, RANTES, SDF-1alpha, or MDC, and the combination of RANTES+HIVgp120IIIB, SDF-1alpha+HIVgp120IIIB, or MDC+HIVgp120IIIB. Food and water intake was measured every day during administration, and 24 and 48 h after the last administration. Rats were also weighed the first and the last day of experiment in order to detect the impact of these treatments in the body weight. HIVgp120IIIB significantly decreased food and water intake. These rats gain less weight than the control (vehicle) and chemokines-treated subjects with exception of those treated with SDF-1alpha that also gain less weight. In addition, HIVgp120 deteriorated motor control. HIVgp120IIIB effects on food and water intake, and motor control were prevented by these chemokines. HIVgp120+RANTES, HIVgp120+SDF-1alpha, and SDF-1alpha alone induced hyperalgesia. Results suggest an interaction between HIVgp120 and the chemokine system to generate the HIV-wasting syndrome, the motor abnormalities and changes in pain perception.

Animals↗