Non-painful sensory phenomena after spinal cord injury. (41/11014)

OBJECTIVES: Non-painful sensory phenomena or "phantom" sensations are common after spinal cord injury. However, the physiological mechanisms responsible for these sensations are poorly understood. The aim of this study, therefore, was to document in a prospective fashion the time course, prevalence, and features of non-painful sensory phenomena after spinal cord injury, and to determine whether there was a relation between the presence of these sensations and completeness, level of injury, and type of spinal cord injury. METHODS: Patients admitted to an acute spinal injuries unit were interviewed after admission and at several time points over a 2 year period to determine the presence and characteristics of non-painful sensations. Sensations were divided into simple and complex, with complex referring to sensations that incorporated a sensation of volume, length, posture, or movement. RESULTS: The present study showed that the large majority (90%) of patients experience either type of sensation and most complex sensations (60%) are first experienced within 24 hours after the injury. Complex sensations were more common in those patients who had complete spinal cord injuries. The presence of either type of sensation did not seem to be related to the level of injury or the type of injury (cord syndrome). A relatively small proportion (22%) of patients reported that the postural sensations were related to their position at the time of injury and sensations were more commonly related to a familiar, comfortable, or often used position before the spinal cord injury. CONCLUSION: Complex sensations such as postural illusions seem to be due to functional changes in the CNS that may occur almost immediately after spinal cord injury. These sensations may be related to a strong sensory memory "imprint" that has been established before injury.  (+info)

Nafamostat mesilate, a kallikrein inhibitor, prevents pain on injection with propofol. (42/11014)

We have examined the preventative effect of nafamostat mesilate, a kallikrein inhibitor, on pain on injection with propofol in a randomized, double-blind study. A control group (n = 110) and a nafamostat (n = 103) group received 5% glucose 0.02 ml kg-1 and nafamostat 0.02 mg kg-1 diluted with 5% glucose, respectively, followed 1 min later by 1% propofol injected at a rate of 200 mg min-1. Pain scores recorded during injection of propofol were significantly less in the nafamostat than in the control group. In another 10 patients, blood concentrations of nafamostat were measured after administration of nafamostat 0.02 mg kg-1 i.v. Mean nafamostat concentration 1 min after injection was 0.1 (SD 0.05) mumol litre-1, which is sufficient to inhibit plasma kallikrein activity. We conclude that pretreatment with nafamostat 0.02 mg kg-1 significantly reduced pain on propofol injection and this effect may be caused by a reduction in kallikrein activity.  (+info)

Somatotopic activation of opioid systems by target-directed expectations of analgesia. (43/11014)

We induced specific expectations of analgesia on four different parts of the body to understand how endogenous opioid systems are activated by expectancies. The left hand, right hand, left foot, and right foot were simultaneously stimulated by means of a subcutaneous injection of capsaicin, which produces a painful burning sensation. Specific expectations of analgesia were induced by applying a placebo cream on one of these body parts and by telling the subjects that it was a powerful local anesthetic. In such a way, expectancy of the anesthetic effect was directed only toward the part on which the placebo cream was applied. We found that a placebo analgesic response occurred only on the treated part, whereas no variation in pain sensitivity was found on the untreated parts. If the same experiment was performed after an intravenous infusion of the opioid antagonist naloxone, this highly spatial-specific placebo response was totally abolished, indicating that it was completely mediated by endogenous opioid systems. These findings show that a spatially directed expectation of pain reduction is capable of inducing a specific effect only on the part of the body which is the target of the expectation. Most important, this specific effect is mediated by endogenous opioids, indicating that placebo-activated opioids do not act on the entire body but only on the part where expectancy is directed. This suggests that a highly organized and somatotopic network of endogenous opioids links expectation, attention, and body schema.  (+info)

Prolonged analgesic effect of ketamine, an N-methyl-D-aspartate receptor inhibitor, in patients with chronic pain. (44/11014)

We examined the role of N-methyl-D-aspartate (NMDA) receptors in chronic (pathological) pain in humans by using the NMDA receptor antagonist ketamine as a probe. Thirty patients with neuropathic pain in the trigeminal area were given an i.m. injection of ketamine 0.4 mg/kg combined with midazolam 0.05 mg/kg. Pethidine 1.0 mg/kg served as a control. Three different response patterns were observed. Ketamine caused a long-term (6-24 h) analgesic effect partly dissociated from the mental side effects in 8 of the 26 patients who completed the study; these patients also had a slight analgesic effect of pethidine. In nine patients, ketamine caused a short-lasting (<2 h) analgesic effect closely associated with the mental side effects, whereas pethidine caused little or no analgesia. The remaining nine patients did not experience any reduction of pain after either drug in spite of characteristic side effects. One week after the i.m. challenge the patients received either 4.0 mg/kg ketamine hydrochloride or placebo capsules to be taken orally as a nightly dose for three consecutive nights. Five of the eight patients who had a long-term analgesic effect of the i.m. challenge reported decreased pain on days after ketamine. None of the others reported an analgesic effect. The phenomenon of long-term depression of pain in a subgroup of patients was thus confirmed when ketamine was given p.o. These findings indicate that NMDA receptors are involved in the perception and maintenance of pathological pain in some patients. In others, pain appears to be mediated by NMDA receptor-independent mechanisms. We suggest that NMDA receptor-independent transmission in central pain pathways may contribute to the reduced efficiency of analgesic drugs often seen in chronic pain states.  (+info)

Pharmacokinetics of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in healthy male volunteers. (45/11014)

AIMS: The aim of this open, randomised, crossover, parallel-group study was to compare the pharmacokinetics and neutrophil responses of lenograstim when administered subcutaneously (s.c.) and intravenously (i.v.). METHODS: A total of 27 healthy male volunteers was recruited. Lenograstim doses (0.5, 2, 5, or 10 microg kg(-1)) were administered s.c. or i.v. once-daily for 5 days, and then, after a 10-day washout period, vice versa for a further 5 days. Lenograstim concentrations and absolute neutrophil counts (ANCs) were measured predosing and postdosing on days 1 and 5. RESULTS: Maximum serum concentrations of lenograstim were higher following i.v. dosing (mean 5.2-185.5 vs 0.7-30.0 ng ml(-1) after s.c. dosing on day 1) and attained sooner (median 0.5-0.8 vs 4.7-8.7 h on day 1). However, apparent elimination half-lives of lenograstim were longer following s.c. dosing (mean 2.3-3.3 vs 0.8-1.2 h after i.v. dosing on days 1 and 5). ANCs increased in a dose-dependent manner with both routes of lenograstim, but more prolonged rises and higher ANC peaks were attained following s.c. doses. ANCs peaked on day 6 following 5 microg kg(-1) s.c. doses (mean peak=26.3x10(9) cells l(-1)), but on day 2 after 5 microg kg(-1) i.v. doses (mean peak = 12.4 x 10(9) cells l(-1)). Irrespective of route, the most common adverse events were headaches and back/spine pain; at doses of up to 5 microg kg(-1) these were mild and generally well tolerated. CONCLUSIONS: While supporting the use of both s.c. and i.v. administered lenograstim to treat neutropenia, these results demonstrate that neutrophil responses are more sustained and prolonged with the s.c. route.  (+info)

Gene for pain modulatory neuropeptide NPFF: induction in spinal cord by noxious stimuli. (46/11014)

Neuropeptides FF (NPFF), AF (NPAF), and SF (NPSF) are homologous amidated peptides that were originally identified on the basis of similarity to the molluscan neuropeptide FMRF-amide. They have been hypothesized to have wide-ranging functions in the mammalian central nervous system, including pain modulation, opiate function, cardiovascular regulation, and neuroendocrine function. We have cloned the NPFF gene from human, bovine, rat, and mouse, and show that the precursor mRNA encodes for all three of the biochemically identified peptides (NPFF, NPAF, and NPSF). We demonstrate that NPFF precursor mRNA expression by Northern analysis and map sites of expression by in situ hybridization. We confirm the validity of the in situ hybridization by showing that its distribution in the brain and spinal cord matches the distribution of NPFF and NPSF immunoreactivity. We go on to show that the mRNA levels (as measured by in situ hybridization) in the spinal cord can be up-regulated by a model for inflammatory pain (carrageenan injection), but not by a model for neuropathic pain (lumbar nerve ligation). Our results confirm the evolutionary conservation of NPFF, NPAF, and NPSF neuropeptide expression in mammalian brain. They also provide a context for the interpretation of the pain-sensitizing effects of injections of these peptides that have been previously reported. Our results support a model for the role of these peptides in pain regulation at the level of the spinal cord.  (+info)

Plantar fasciitis and other causes of heel pain. (47/11014)

The most common cause of heel pain is plantar fasciitis. It is usually caused by a biomechanical imbalance resulting in tension along the plantar fascia. The diagnosis is typically based on the history and the finding of localized tenderness. Treatment consists of medial arch support, anti-inflammatory medications, ice massage and stretching. Corticosteroid injections and casting may also be tried. Surgical fasciotomy should be reserved for use in patients in whom conservative measures have failed despite correction of biomechanical abnormalities. Heel pain may also have a neurologic, traumatic or systemic origin.  (+info)

Primary gastric T-cell lymphomas: report of two cases and a review of the literature. (48/11014)

To understand more fully the clinicopathological features of primary gastric T-cell lymphomas (PGTL), we report two cases of PGTL and review the literature. The present cases were not associated with human T-cell leukemia virus type 1 (HTLV-1) and were at clinical stage IIE. In both cases, T-cell origin of the lymphoma cells was diagnosed immunohistochemically. The clinical courses of these two cases were different: one followed a very aggressive clinical course and the patient died 6 months after the diagnosis, whereas the other patient survived more than 2 years without adjuvant chemotherapy. Clinicopathological features of 23 patients with PGTL are summarized with regard to their differences from primary small intestinal T-cell lymphomas (PSITL) and by association with HTLV-1. The median age at onset of PGTL was 58 years. The gender ratio was male-dominant (M:F = 2.3:1). About two-thirds (10 of 17) of PGTL cases had evidence of HTLV-1 infection. The most common presenting symptom for PGTL was upper abdominal discomfort and/or pain (76%), whereas that in PSITL was weight loss (61%) and diarrhea (42%). Typical lesions for PGTL were large ulcerations at the corpus to antrum. Neoplastic cells had no typical morphological characteristics for PGTL including HTLV-1-associated cases. CD3+4+8- was the most frequently observed surface phenotype of PGTL cells. Laboratory findings at diagnosis were not informative. Most patients were treated by gastrectomy with or without chemotherapy. PGTL, excluding that with HTLV-1, showed better prognosis than PSITL, although PGTL with HTLV-1 had a poorer prognosis.  (+info)