Diclofenac epolamine topical patch for the treatment of pain.

Topical nonsteroidal anti-inflammatory drugs produce local pain relief while avoiding systemic adverse events, thanks to minimal systemic absorption. This review evaluates the effectiveness and safety of a topical diclofenac preparation, diclofenac epolamine (DHEP) patch 1.3% or diclofenac epolamine patch with heparin as excipient (DHEP+H) in treating mild-to-moderate pain. DHEP patch was associated with significant pain relief and improved function in numerous pain conditions, from minor soft tissue injuries to osteoarthritis and myofascial pain syndromes. Tolerability was good-to-excellent in all studies, with no serious adverse events. DHEP+H further improved efficacy without affecting tolerability. This patch is effective and safe for localized mild-to-moderate somatic pain.

Psoriasis and migraine.

BACKGROUND: Psoriasis and migraine share several pathogenetic mechanisms due to systemic inflammation, which increase the risk of developing cardiovascular disease. OBJECTIVE: Our aim was to investigate the prevalence of migraine with (MA) and without aura (MO) in the psoriatic population, investigating a possible new comorbidity of the psoriatic disease. METHODS: We referred 68 psoriatic patients to a nine questions survey formulated on the basis of the International Headache Society (IHS) diagnostic criteria for migraine. Then, in the case of MA, the mean monthly number of migraine crises was assessed. Data of psoriatic patients were then compared with those of a psoriasis-free control group composed of 235 migraine patients (with and without aura). RESULTS: A clinical diagnosis of migraine was performed in 32 psoriasis patients with a great prevalence in women (F: 87.50% - M: 12.5%). Moreover, we found a much higher prevalence (62.5%) of MA, with the remaining 37.5% diagnosed with MO. Comparing the prevalence of MA between psoriasis + migraine patients and the control group we observed a statistical significative difference (P < 0.0001); furthermore, the number of MA crises was significantly higher (P < 0.0001) in patients with psoriasis with respect to the MA control group. CONCLUSIONS: We showed a significant association between psoriasis and migraine, especially MA, probably due to common pathogenetic mechanisms, but further studies are needed to assess their interplay in developing cardiovascular diseases.

Controlling pain in the post-operative setting.

BACKGROUND AND AIMS: Post-operative pain (POP) is a form of acute, intense pain experienced in the period following surgery, whose adequate control is often problematic. This paper reviews determinants and characteristics of POP, together with rationale and current protocols for its management. DETERMINANTS/CONSEQUENCES OF POP: Main determinants of POP are the type of intervention and the disease motivating surgery, though other factors related to patient (age, pain threshold, socio-cultural factors, personality) and setting (pre-operative information, relationship with medical staff) may also influence its perception. POP control is essential to relieve suffering but also to prevent dangerous consequences on organ systems, e.g., reduced cough, atelectasis, increased myocardial oxygen consumption and ischemia, constipation, urinary retention, reduced musculoskeletal mobility and increased risk of deep venous thrombosis. MANAGEMENT OF POP: Constant assessment of pain intensity is recommended for optimal POP control. This is mostly achieved pharmacologically with monitoring of side-effects. Multi-modal analgesia is recommended, combining different drug classes, e.g., an opioid (morphine, pethidine, fentanyl, tramadol, codeine) with a non-opioid (NSAID; Cox-2 inhibitor), delivered through various routes, and including neuraxial use of local anesthetics (bupivacaine, ropivacaine) alone or in combination with other drugs, nerve blocks, antihyperalgesics (ketamine, dextromethorphan) and techniques such as patient-controlled analgesia (PCA) and pre-emptive analgesia. An efficient organization of pain services is also recommended. CONCLUSION: Acute post-surgical pain represents a crucial problem, but the multimodal therapeutic approach has enhanced the efficacy of pain-control while minimizing side-effects of each modality. Further improvement of POP control will necessarily involve better organization of pain services.

Submaximal aerobic exercise with mechanical vibrations improves the functional status of patients with chronic fatigue syndrome.

AIM: Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of uncertain aetiology and other nonspecific symptoms. Typically CFS patients complain of a severe fatigue made worse by exercise, with a consistent reduction of working activity. A physical deconditioning could explain CFS features as well as a neuromuscular dysfunction, of central or peripheric origin. METHODS: Ten CFS patients were enrolled in a protocol of a rehabilitative treatment over a six-month period: they underwent a submaximal and predominantly aerobic exercise with a reduced O2 consumption using a Galileo 2000 system that provides mechanical vibrations characterised by sinusoid vertical sollecitations. Before and after such treatment, all patients underwent a pressure pain thresholds profile, an evaluation of physical and psychosocial parameters using the visual analogue scale (VAS) of Scott-Huskisson, and a muscle performance analysis by the CIBEX 6000 dynamometer. RESULTS: After the six-month period of study there was an overall improvement of the above described parameters as compared to the basal determinations. CONCLUSION: We conclude that the rehabilitative exertion provides an useful treatment for CFS patients particularly to realize an effective training of the explosive strength.

Effects of topical diclofenac (DHEP plaster) on skin, subcutis and muscle pain thresholds in subjects without spontaneous pain.

The aim of this study was to determine whether topical application of diclofenac hydroxyethylpyrrolidine (DHEP) modifies somatic pain sensitivity in subjects without spontaneous pain. Twenty male subjects (aged 19-40 years), who had not reported any pain for at least 1 month, underwent measurement of pain thresholds to bilateral electrical stimulation in the quadriceps muscle and overlying subcutis and skin. Following the double-blind study design, one diclofenac adhesive plaster (13 x 10 cm; 180 mg DHEP) was then applied over one quadriceps while a matched placebo plaster was placed contralaterally. Each subject was given two other plasters (diclofenac and placebo) and instructed to substitute those over the quadriceps after 12 h and to wear them for a further 12 h. Thirty minutes after removal of the second plasters, thresholds. were remeasured in all subjects as on the previous day. Thresholds at the first evaluation were within normal range in nine subjects (group 1) and below normal in muscle (hyperalgesia) in the remaining 11 (group 2). No significant changes were observed in skin or subcutis thresholds after diclofenac or placebo treatment in either group. In contrast, muscle thresholds significantly increased after diclofenac compared with placebo treatment (group 1: p < 0.05; group 2: p < 0.007); the increase was significantly higher in group 2 than in group 1 (p < 0.002). Topical application of diclofenac had a selective hypoalgesic effect on muscles, which was more pronounced in the case of hyperalgesia. These results suggest that the preparation is particularly effective in the treatment of algogenic conditions of deep somatic tissues.

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).

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.

Uterine inflammation as a noxious visceral stimulus: behavioral characterization in the rat.

We have developed a model of uterine inflammation in the rat. The purpose of this study was to characterize the behavioral manifestations of uterine pain. Mustard oil was injected into one uterine horn to produce chemical inflammation. Control rats were sham-operated. Non-stop videotape recording was performed for 7 days to monitor rat behavior. Rats with uterine inflammation showed abnormal behavior during the first 4 days (hunching, hump-backed position, licking of the lower abdomen, repeated waves of contraction of the ipsilateral oblique musculature with inward turning of the ipsilateral hindlimb, stretching, squashing of the lower abdomen against the floor) suggestive of visceral pain and evidence of flank muscle hyperalgesia over 7 days indicative of referred visceral pain. This model resembles closely a state of inflammatory uterine pain and will allow to gain further insight into the neural processes which contribute to visceral nociception.

Central neuronal changes in recurrent visceral pain.

Repeated colics from urinary calculosis produce referred muscle hyperalgesia whose extent is proportional to the number of colics. The pathophysiology of this hyperalgesia was investigated in electrophysiological studies (spinal cord recordings) on an animal model of artificial ureteral calculosis. Stone-implanted rats show both visceral pain episodes and muscle hyperalgesia of the ipsilateral lumbar musculature; the extent of hyperalgesia is a function of the number of episodes. In the dorsal horn of stone-rats compared to controls the following were found: a) significantly higher percentages of neurons driven by stimulation of the hyperalgesic muscle, of spontaneously active cells with muscle input and of neurons with muscle input with a low mechanical threshold of activation, and b) a significantly higher frequency of background activity of spontaneously active cells with muscle input. These findings were proportional in extent to the number of visceral episodes presented by the rats before recordings; in cases of an extremely high number (> 50), several neurons also displayed abnormal activity, i.e. permanent short rhythmic bursts. These changes reflect a state of central sensitization and are probably due to the abnormal inflow from the affected ureter which facilitates the central effect of muscular input, thus accounting for the referred hyperalgesia. The degree of sensitization appears to be a function of the repetition of the visceral afferent barrage.

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).