Metabolic changes induced by maximal exercise in human subjects following L-carnitine administration.

In double-blind cross-over experiments, ten moderately trained male subjects were submitted to two bouts of maximal cycle ergometer exercise separated by a 3 day interval. Each subject was randomly given either L-carnitine (2 g) or placebo orally 1 h before the beginning of each exercise session. At rest L-carnitine supplementation resulted in an increase of plasma-free carnitine without a change in acid-soluble carnitine esters. Treatment with L-carnitine induced a significant post-exercise decrease of plasma lactate and pyruvate and a concurrent increase of acetylcarnitine. The determination of the individual carnitine esters in urine collected for 24 h after the placebo exercise trial revealed a decrease of acetyl carnitine and a parallel increase of a C4 carnitine ester, probably isobutyrylcarnitine. Conversely, acetylcarnitine was strongly increased and C4 compounds were almost suppressed in the L-carnitine loading trial. These results suggest that L-carnitine administration prior to high-intensity exercise stimulates pyruvate dehydrogenase activity, thus diverting pyruvate from lactate to acetylcarnitine formation.

[Prevalence of obesity, overweight and hypertension in children and adolescents from Abruzzo, Italy]. / Prevalenza di obesità, sovrapeso e ipertensione nei bambini e adolescenti della provincia di Pescara.

The present survey was aimed at determining the prevalence of overweight, obesity, hypertension, their correlation and the association with gender, age and provenience, in the pediatric population of Pescara province, Italy. During the academic year 2001-2002, the body mass index (BMI) and blood pressure of 15.612 scholars aged 6-14 years (mean age 9.9), coming from all province schools, have been measured. Two scales have been used to define obesity and overweight status (one developed by the National Center for Health Statistics--NCHS--the other by Cacciari et al.); while hypertension has been attributed using National Institute of Health curves. Several multiple logistic regression models have been fitted to analyze data. According to NCHS standards, the prevalence of childhood and adolescence overweight and obesity was, respectively, 40.6% and 19.5%. Using curves by Cacciari, the prevalence were 33.3% and 7.7%. Hypertensive subjects were 11.1%. With both scales, the prevalence of weight problems widely decreased after 12 years of age, and either obesity or overweight were significantly related with male sex, hypertension and rural area residence. A strong independent association was found between living inside the city and hypertension. Although the differences in the dimension of the problem "overweight" according to the used scale, and a potential overestimation of hypertension must be taken into account, the overall data suggest an urgent need, especially for primary school children, of preventive interventions aimed at reducing both overweight and blood pressure.

Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a poorly understood disease characterized by mental and physical fatigue, most often observed in young white females. Muscle pain at rest, exacerbated by exercise, is a common symptom. Although a specific defect in muscle metabolism has not been clearly defined, yet several studies report altered oxidative metabolism. In this study, we detected oxidative damage to DNA and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total glutathione plasma levels. From these results we hypothesize that in CFS there is oxidative stress in muscle, which results in an increase in antioxidant defenses. Furthermore, in muscle membranes, fluidity and fatty acid composition are significantly different in specimens from CFS patients as compared to controls and to patients suffering from fibromyalgia. These data support an organic origin of CFS, in which muscle suffers oxidative damage.

Pain from renal/ureteral calculosis: evaluation of sensory thresholds in the lumbar area.

Patients with unilateral renal/ureteral calculosis who had suffered a few painful attacks were examined. In the pain-free period, muscular, subcutaneous and cutaneous sensory thresholds to electrical stimulation were measured in the lumbar region (metamer L1) on both sides: (1) pain thresholds were lower on the affected side with respect to both the contralateral side and control thresholds recorded in normal subjects; (2) the greatest decrease in threshold was in the muscle (even the sensation of sustained contraction was no longer detectable), followed by subcutaneous tissue, and the smallest decrease was in the skin.

Pain threshold variations in somatic wall tissues as a function of menstrual cycle, segmental site and tissue depth in non-dysmenorrheic women, dysmenorrheic women and men.

Pain symptoms of many disorders are reported to vary with menstrual stage. This study investigated how pain thresholds to electrical stimulation of the skin, subcutis and muscle tissue varied with menstrual stage in normal women and compared these variations with those in women with dysmenorrhea and in healthy men at matched intervals. Thresholds of the three tissues were measured four times during the course of one menstrual cycle at four sites. Two of the sites were on the abdomen within the uterine viscerotome (abdomen-rectus abdominis, left and right) and two were outside it on the limbs (leg-quadriceps, arm-deltoid). Calculated from the beginning of menstruation (day 0), the menstrual phases studied were menstrual (days 2-6), periovulatory (days 12-16), luteal (days 17-22) and premenstrual (days 25-28). Spontaneous pain associated with menstruation was measured from diary estimates on a VAS scale. Whereas the highest thresholds always occurred in the luteal phase regardless of segmental site or stimulus depth, the lowest thresholds occurred in the periovulatory stage for skin, whereas those for muscle/subcutis occurred perimenstrually. Dysmenorrhea accentuated the impact of menstrual phase. For non-dysmenorrheic women menstrual trends were significant only in abdominal muscle and subcutis, but for dysmenorrheic women the trends were also significant in abdominal skin and in limb muscle and subcutis. Dysmenorrhea also lowered thresholds mainly in muscle and sometimes in subcutis, but never in skin, with the greatest hyperalgesic effects in left abdominis muscle. Abdominal sites were more vulnerable to menstrual influences than limb sites. Muscle thresholds, but not skin or subcutis thresholds, were significantly lower in abdomen than in limbs, particularly in dysmenorrheic women. The amount of abdominal muscle hyperalgesia correlated significantly with the amount of spontaneous menstrual pain. Only minor sex differences were observed for pain thresholds of the arm and leg, but there was a unanimous refusal by men, but not by women, to be tested at abdominal sites. These results indicate that menstrual phase, dysmenorrhea status, segmental site, tissue depth and sex all have unique interacting effects on pain thresholds, thus adding more items to the lengthy and still-growing list of biological factors that enter into an individual's judgment of whether or not a stimulus is painful.

A multicentre double-blind investigation comparing nimesulide and naproxen in the treatment of minor sport injuries.

A total of 660 patients with minor traumatic sport-related lesions of soft tissues were recruited to a randomised double-blind 7-day study to evaluate the efficacy and the tolerability of oral nimesulide (300 mg/day) in comparison with naproxen (750 mg/day). Both drugs were similarly effective in reducing the degree of oedema and intensity of pain, with most patients experiencing remission, which allowed resumption of regular sporting activities. Both drugs were generally well tolerated, although gastrointestinal intolerance was more frequently associated with naproxen therapy.

Effects of a standardized ginseng extract combined with dimethylaminoethanol bitartrate, vitamins, minerals, and trace elements on physical performance during exercise.

The subjects of this double-blind, randomized, crossover study were 50 healthy male sports teachers aged 21 to 47 years. Every day for six weeks each subject received two capsules of a preparation containing ginseng extract, dimethylaminoethanol bitartrate, vitamins, minerals, and trace elements, or two capsules of placebo. The subjects then performed an exercise test on a treadmill at increasing work loads. The total work load and maximal oxygen consumption during exercise were significantly greater after the ginseng preparation than after placebo. At the same work load, oxygen consumption, plasma lactate levels, ventilation, carbon dioxide production, and heart rate during exercise were significantly lower after the ginseng preparation than after placebo. The effects of ginseng were more pronounced in the subjects with maximal oxygen consumption below 60 ml/kg/min during exercise than in the subjects with levels of 60 ml/kg/min or above. The results indicate that the ginseng preparation increased the subjects' work capacity by improving muscular oxygen utilization.

Muscular pain caused by isometric contraction: evaluation of pain through visual analog scale.

Pain caused by muscular isometric contraction was investigated through use of the visual analog scale. The results demonstrate that the latency time and the time to reach maximum intensity are inversely proportional to the amount of the load; therefore increase of pain is linear. The high statistical significance of the results suggests that pain by isometric contraction could be a comparison test for somatic pain evaluation in spontaneous pathological conditions.

Effects of aerobic exercise on muscular pain sensitivity.

Muscular pain sensitivity after aerobic exercise was investigated in ten healthy men aged 20 to 30 years in four tests at five-day intervals to determine if previous aerobic work leads to a hyperalgesic status. The intensity of pain was recorded, by visual analog scale, every 30 seconds after the injection of 1 ml of 10% and of 20% sodium chloride hypertonic solution, both during basal conditions, and 1 ml of 10% sodium chloride hypertonic solution 1 and 60 minutes after 30 minutes of submaximal rectangular exercise. The injection of 10% sodium chloride solution 60 seconds after exercise gave rise to a clear increase in pain, similar to that induced by the 20% sodium chloride solution given during basal condition. This observation shows that submaximal exercise produces a hyperalgesic state in the active muscle. This hyperalgesia probably explains the clinical manifestation of latent algogenic triggers during physical activity.

Effects of diflunisal on cutaneous sensory and pain thresholds.

The analgesic activity of diflunisal was evaluated through the measurement of cutaneous sensory and pain thresholds after electrical stimulation. Twelve healthy volunteers were examined at baseline and five hourly intervals after oral administration of 500 mg and 1 gm of diflunisal. The results showed that the sensory threshold was not modified by diflunisal, but that the pain threshold was significantly increased two and three hours after 500 mg of diflunisal and one, two, and three hours after 1 gm of diflunisal. At two hours the pain threshold was significantly higher after 1 gm than after 500 mg of diflunisal. It is concluded that diflunisal produces an actual increase of the pain threshold in healthy human subjects and that the amplitude, latency, and duration of its effect are dose related.

Changes in visceral pain reactivity as a function of estrous cycle in female rats with artificial ureteral calculosis.

This study examined estrous differences in the characteristics of behavioral crises of visceral pain in female rats video-taped throughout a 4-day period after implantation of an artificial stone in one ureter. All animals continued to have a regular cycle after ureteral surgery. In the recording period, the percentage of time spent in crises was significantly higher during metestrus/diestrus (M/D) than during proestrus/estrus (P/E) (P < 0.001, chi2-test). Mean duration and complexity of crises were slightly higher in M/D than in P/E, but the difference was not significant. The results in this animal model show an enhancement of ureteral pain sensitivity in M/D, a finding in line with the clinical observation, in fertile women with urinary calculosis, of a greater incidence of colics in the perimenstrual period (equivalent to M/D in rats).

Pre-emptive analgesia in rats with artificial ureteric calculosis. Effects on visceral pain behavior in the post-operative period.

'Pre-emptive' analgesia is a controversial issue in both the clinical and experimental literature on pain. This paper investigates the effect of chronic (4 days) administration of morphine or ketoprofen initiated pre- or post-operatively on behavioral indicators of visceral pain and referred hyperalgesia in an animal model of artificial ureteric calculosis. In the morphine experiment, female Sprague-Dawley rats were treated i.p. with saline or morphine sulphate (2.5 or 5 mg/kg/day) starting either 45 min before or 45 min after surgery (pentobarbital anesthesia) for stone implantation in the left ureter, until the 4th day after intervention. Behavioral crises of ureteric pain were recorded (video-tape) in all rats over 4 days post-operatively. Number, duration and complexity of crises of stone-rats were significantly and dose-dependently reduced by administration of morphine with respect to saline in an identical manner for the pre- and post-operative treatment. In the ketoprofen experiment, rats were given saline or ketoprofen (15 mg/kg/day, in 3 i.p. injections per day) starting either pre- or post-operatively with the same paradigm as for the morphine study. Vocalization thresholds to electrical stimulation of the left oblique musculature were measured daily for 3 days pre- and 4 days post-operatively. Muscle hyperalgesia (post-operative decrease in threshold with respect to pre-stone implantation) was significantly reduced in extent and duration in ketoprofen with respect to saline-injected animals but no difference was found between the pre- and post-operative treatment. It is concluded that pre-emptive administration of morphine or ketoprofen has no advantage in reducing behavioral indicators of visceral pain and referred hyperalgesia in this animal model.

Effects of spasmolytic and/or non-steroidal antiinflammatory drugs on muscle hyperalgesia of ureteral origin in rats.

Rats with artificial calculosis of one ureter develop hyperalgesia in the ipsilateral oblique musculature as evidenced by decreased vocalization threshold to electrical muscle stimulation lasting over a week. The aim of the study was to evaluate the effect on this hyperalgesia of spasmolytic anticholinergic and/or non-steroidal antiinflammatory drugs, common therapies for colic pain in humans. Rats implanted with a unilateral ureteral stone were treated for 10 days with: (1) saline; (2) hyoscine-N-butylbromide (15 mg/kg/day i.p.); (3) ketoprofen (15 mg/kg/day); or (4) hyoscine-N-butylbromide + ketoprofen (15 + 15 mg/kg/day). Oblique muscle vocalization thresholds were measured daily for 3 days before and 10 days after operation. Ipsilateral thresholds decreased significantly after stone implantation on: (1) seven days (max. 32%) for saline; (2) one day (max. 20%) for hyoscine-N-butylbromide; (3) one day (max. 18%) for ketoprofen, but did not change significantly for hyoscine-N-butylbromide + ketoprofen. These results indicate a protective effect against muscle hyperalgesia of ureteral origin by spasmolytic and antiinflammatory drugs, maximal when the two treatments are combined.

Changes in activity of spinal cells with muscular input in rats with referred muscular hyperalgesia from ureteral calculosis.

In rats with hyperalgesia of the obliquus externus muscle (OE) from artificial calculosis of the ipsilateral upper ureter, changes in cell activity were studied in the ipsilateral spinal cord (T11-T12) versus control animals. In cases of hyperalgesia of high degree, in the dorsal horn (0-900 microns) the following were found: significantly higher percentages of cells driven by OE stimulation (P < 0.03) and of spontaneously active cells with OE input (P < 0.02); significantly higher frequency of background discharge of cells with OE input (P < 0.002); among cells driven by OE stimulation, significantly higher percentages of neurons with exclusively deep input (P < 0.0006) and of neurons with low mechanical threshold of activation (P < 0.03). In the intermediate region of the cord (900-1600 microns), a significantly higher percentage was found of spontaneously active cells with OE input (P < 0.009) while in the ventral horn (1600-2300 microns) no changes were detected. The results indicate that referred muscle hyperalgesia of high degree is accompanied by a state of central sensitization probably triggered by the abnormal afferent input from the visceral focus.

Modulation of pain and hyperalgesia from the urinary tract by algogenic conditions of the reproductive organs in women.

This study investigated the impact of algogenic conditions of the reproductive organs upon urinary pain perception in women. A 5-year survey was conducted among 69 fertile women with calculosis of one upper urinary tract via an ad-hoc questionnaire. At both retrospective (3 years) and prospective (2 years) investigation, dysmenorrheic women (D) reported more colics than non-dysmenorrheic women (ND) (P<0.001) and women with previous dysmenorrhea treated with estroprogestins (DH)(P<0.05). Pain thresholds (electrical stimulation) of the oblique musculature ipsilateral to the stone (L1, site of referred hyperalgesia from upper urinary tract) were lower in D than in ND (P<0.01) and DH (P<0.05). Calculosis women with asymptomatic endometriosis / ovarian cysts also reported more colics (6-month prospective study) and greater threshold lowering (P<0.05) than women with calculosis alone. The results show enhancement of urinary pain / hyperalgesia by both manifest and latent algogenic conditions of the female reproductive organs. This enhancement could derive from neuronal sensitization in spinal segments of common projection of the two visceral districts (T10-L1).

Muscular hyperalgesia and hypoalgesia after stimulation of the ureter in rats.

Vocalization electric thresholds were measured bilaterally in muscles of the lower back and in the tail after electrical stimulation of the left ureter in rats implanted with electrodes. 'Painful' stimulation immediately produced a hyperalgesia lasting about half an hour in the left lower back muscles and tail, followed by a 10 min hypoalgesia limited to the back muscles. No modification or only a delayed hypoalgesia appeared in the right muscle. Strong but 'non-painful' stimulation produced no effect or gave rise to an immediate hypoalgesia in the left muscle. Weak non-painful stimulation produced a delayed hypoalgesia in the tail.

Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome.

Patients with chronic fatigue syndrome (CFS) mainly complain of symptoms in the musculoskeletal domain (myalgias, fatigue). In 21 CFS patients the deep (muscle) versus superficial (skin, subcutis) sensitivity to pain was explored by measuring pain thresholds to electrical stimulation unilaterally in the deltoid, trapezius and quadriceps and overlying skin and subcutis in comparison with normal subjects. Thresholds in patients were normal in skin and subcutis but significantly lower than normal (hyperalgesia) in muscles (P < 0.001) in all sites. The selective muscle hypersensitivity corresponded also to fiber abnormalities at muscle biopsy (quadriceps) performed in nine patients which were absent in normal subjects (four cases): morphostructural alterations of the sarchomere, fatty degeneration and fibrous regeneration, inversion of the cytochrome oxidase/succinate dehydrogenase ratio, pleio/polymorphism and monstruosity of mitochondria, reduction of some mitochondrial enzymatic activities and increments of common deletion of 4977 bp of mitochondrial DNA 150-3000 times the normal values. By showing both sensory (diffuse hyperalgesia) and anatomical (degenerative picture) changes at muscle level, the results suggest a role played by peripberal mechanisms in the genesis of CFS symptoms. They would exclude the heightened perception of physiological signals from all districts hypothesized by some authors, especially as the hyperalgesia is absent in skin/subcutis.

Effects of meclofenamic acid in the treatment of lesions deriving from minor traumatology.

The clinical efficacy and tolerability of topical 5% meclofenamic acid gel versus placebo and oral sodium meclofenamate versus sodium naproxen were evaluated in patients affected with minor traumatologies. Ninety patients were studied: 60 were treated with either meclofenamic acid gel or placebo for 10 days, and 30 were administered with either sodium meclofenamate capsules or sodium naproxen capsules for 7 days. The 5% meclofenamic acid gel and its sodium salt in capsules proved significantly more rapid and efficient than did the reference compounds in reducing pain symptomatology. In the patients treated with 5% meclofenamic acid gel, a greater effect was seen as regards rapidity of spontaneous movement and nocturnal pain reduction. In other variables examined, that is, surface and deep hyperalgesia, and swelling and functional restriction, there was also a significantly higher efficacy than with placebo. Confirmation of the therapeutic efficacy of meclofenamic acid (sodium salt) was obtained with the capsule formulation, that was seen to exert a significant analgesic and antiphlogistic action; the onset of this action was particularly rapid. Both formulations of meclofenamic acid (gel and capsules) were found to be well tolerated. Thus, in the examined formulations, meclofenamic acid proved to be a useful tool in the treatment of lesions in the minor traumatology category.

Myofascial pain syndromes: clinical and pathophysiological aspects.

The criteria for performing a diagnosis of myofascial pain syndromes caused by trigger points (TrPs) are defined and the clinical features of pain and related phenomena due to these syndromes are examined together with the sensory modifications of the parietal tissues at TrPs and target level in the case of both active and latent TrPs. The factors presumably responsible for the occurrence of TrPs in myofascial structures are then considered, with particular emphasis on the microtraumatic event caused by biomechanical alterations during movement, evaluated by the analysis of the ground-foot reaction. With this respect, some examples of myofascial pain syndromes of the lower limbs are reported in which the correction of these alterations, performed via dynamic orthosis, produces a long-lasting remission of the subjective and objective symptomatology.

Myofascial pain syndrome of the peroneus longus: biomechanical approach.

OBJECTIVE: The aim of the study was to investigate the role played by anatomical (lower limb length discrepancy) and biomechanical (alterations in the dynamics of movement) factors in the pathophysiology of myofascial pain syndrome (MPS) of the peroneus longus. DESIGN: Patients affected with MPS of the peroneus longus of one side were submitted to either correction of their lower limb discrepancy by heel lift (6 patients) or normalization of altered biomechanical parameters during movement, as measured via ground-foot reaction analysis (g-f) by dynamic insoles (6 patients) for 60 days. At days 7, 15, 30, and 60, the effect of treatment was verified on painful symptoms [VAS scale, presence of the active trigger point (TrP) in the muscle] and on g-f parameters [peaks of vertical force (F1 and F3 of Fz) and of lateral shear force (Fx)]. RESULTS: Treatment with heel lift produced a moderate, significant reduction of the spontaneous pain and of the abnormal Fx peak in the affected leg after 7 to 14 days with no further improvement afterward. Treatment with dynamic insoles caused a marked, significant reduction of the pain at 7 days, with complete resolution of the painful symptoms at 30 days and concomitant disappearance of the active TrP in the muscle. It also produced a significant and progressive reduction of the abnormal Fx peak in the affected leg starting at the 7th day and continuing until the 60th day. CONCLUSION: Both anatomical and biomechanical alterations of the dynamics of movement play a role in the painful symptoms of MPS of the peroneus longus, but the biomechanical factor is by far the more prominent.