losartan-potassium and Pain

Lung cancer is a bad prognostic illness with a limited survival and many side effects related to treatment used. Supportive care in cancer attends to enhance patient care among cancer and treatments suffering. Opioids are one of the most important treatments in the management of dyspnoea and pain. Every new drug in supportive care is tested to diminish side effects of treatment like erythropoietin against anemia or aprepitant against emesis. Many trials are developed to enhance this supportive care especially in lung cancer management.

Topics: Algorithms; Analgesics, Opioid; Angiogenesis Inhibitors; Antiemetics; Antineoplastic Agents; Aprepitant; Carcinoma, Bronchogenic; Dyspnea; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Lung Neoplasms; Morphine; Morpholines; Pain; Palliative Care; Prognosis; Recombinant Proteins

Anemia is a common comorbidity in individuals with rheumatoid arthritis (RA). In fact, anemia of the type characterized by low serum iron concentrations in conjunction with adequate iron stores is frequently associated with RA and has served as a model for anemia of chronic disease. A systematic search of the scientific literature published since January 1966 identified 19 articles that reported findings on either the prevalence of anemia in patients with RA or outcomes for patients with anemia and RA. Ten articles addressed the prevalence of anemia in patients with RA. Estimates of the prevalence of mild anemia ranged between 33% and 60%; however, the 2 studies that examined demographics in patients with RA did not identify subpopulations at particular risk for anemia. Twelve articles assessed the impact of the resolution of anemia on symptoms and quality of life (QOL) in patients with RA. For many of the parameters assessed-including swollen, painful, and tender joints, pain, muscle strength, and energy levels-a positive correlation was observed between improvement of symptoms and the resolution of anemia. In addition, 2 studies reported a significant improvement in QOL scores in patients with RA who experienced a response to treatment for anemia. These results suggest that (1) patients with RA who have anemia are likely to have more severe joint disease and (2) if the anemia is successfully treated, the joint disease will likely respond to treatment as well. Whether improvements in QOL and/or joint symptoms occur with improvement of anemia, independent of other signs of an overall response to RA therapy, remains to be determined.

Topics: Activities of Daily Living; Adult; Age Distribution; Anemia; Arthritis, Rheumatoid; Blood Transfusion; Child; Cost of Illness; Erythropoietin; Fatigue; Female; Hand Strength; Humans; Iron; Male; Outcome Assessment, Health Care; Pain; Prevalence; Quality of Life; Risk Factors; Severity of Illness Index; Sex Distribution

Topics: Anemia; Erythropoietin; Humans; Injections, Intravenous; Injections, Subcutaneous; Pain; Pharmaceutical Vehicles; Recombinant Proteins; Renal Dialysis

Sustained erythropoiesis-stimulating agents (ESAs) have recently been identified as the standard therapeutic agent for anemia in patients undergoing peritoneal dialysis (PD). However, few reports have compared pain between various types of sustained ESAs or between administration routes. Furthermore, the change ratio of the dose of sustained ESAs reportedly ranges from 0.8 to 1.3. In the present study, to compare darbepoetin alfa and epoetin beta pegol (a continuous erythropoietin receptor activator [CERA]), we examined the dolorific differences between administration routes and the effect on anemia by using a chjange ratio of 0.8 with darbepoetin alfa in patients with renal anemia undergoing PD.. We randomly assigned 20 patients with stable hemoglobin levels undergoing PD to either a darbepoetin alfa therapy group or a CERA therapy group. Based on a previous report, the change ratio of the CERA group from CERA to darbepoetin alfa therapy was assumed to be 0.8, and therapy was crossed-over to darbepoetin alfa again 2 months later. The dolorific evaluation (pain measurement) used both a face scale and a visual analogue scale. We compared the agents as well as administration routes with respect to pain. We also measured variables related to anemia and iron metabolism.. The change ratio of the CERA group at the start of the study was 0.821. On resumption of darbepoetin alfa therapy 2 months later, the doses of darbepoetin alfa increased. The darbepoetin alfa group showed a stronger tendency for pain, although the difference was not significant. In contrast, subcutaneous administration in the CERA group showed significant pain just after injection. The CERA group, however, showed a significant decrease in hemoglobin levels after 2 months of treatment (p=0.0489). No significant change was found in the hematocrit or the reticulocyte count. There were no significant differences in iron metabolism, as shown by serum iron levels and total iron-binding capacity, in either group. However, serum ferritin levels showed a tendency to decrease in the darbepoetin alfa group.. No significant difference in pain was found between darbepoetin alfa and CERA therapies, but a significant difference in pain was noted between administration routes, just after injection, in the CERA group. The results also suggest that a change ratio of 0.8 from darbepoetin alfa to CERA is low for managing anemia.

Topics: Aged; Anemia; Biomarkers; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Japan; Male; Middle Aged; Pain; Pain Measurement; Peritoneal Dialysis; Polyethylene Glycols; Prospective Studies; Time Factors; Treatment Outcome

Subcutaneous injection of erythropoiesis-stimulating agents for the correction of anemia associated with chronic kidney disease is well recognized. Different delivery devices are available, although their impact on patient-reported outcomes is limited.. Subcutaneous delivery of darbepoetin alfa via an autoinjector prefilled pen (PFP) and prefilled syringe (PFS) were compared and assessed according to patient-rated preferences and perceptions.. In this single-center, randomized, open-label, double-crossover study, patients continued using the PFS for 4 injections or were switched to the PFP for the same number of injections, after which they were switched to the alternative device. Following further 4 injections using the new device, patients were switched back to the initial device. Questionnaires were administered at the end of each series of injections for each device and at the start and end of the study.. For overall device preference, the majority (62%) of patients responded with PFP, whereas 32% preferred the PFS mode of delivery. This preference for PFP was driven by a perception of increased convenience and ease of use compared with PFS. No significant differences in pain scores were noted between the 2 devices. Most patients rated both devices as being "easy" or "extremely easy" to use and were either "satisfied" or "extremely satisfied.". When given the choice, most patients preferred the PFP mode of administration compared with PFS due to convenience and ease of use. ClinicalTrials.gov identifier: ACTRN12611000839909.

Topics: Aged; Anemia; Cross-Over Studies; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Subcutaneous; Male; Middle Aged; Pain; Patient Preference; Patient Satisfaction; Renal Insufficiency, Chronic; Surveys and Questionnaires

Although immediate pain sensation at the injection site is reported by patients, only limited data on comparison of pain at the injection site between erythropoiesis stimulating agents are available. Therefore, we compared the effect of subcutaneous epoietin-beta on immediate pain sensation to that of subcutaneous darbepoietin-alpha in a double blind, randomized controlled study. Adult patients, aged 18 - 75 years, treated with peritoneal dialysis or with stage 4 chronic kidney disease who in our unit are treated with subcutaneous darbepoietin-alpha for renal anemia for at least 3 months, were eligible for the study. After informed consent, patients received on one day four subcutaneous injections, two in each upper leg, in a fixed sequence, blinded to the patient and blinded to the investigator. Injections contained in a random order single dose epoietin-beta (0,3 ml = 4000 IU), darbepoietin-alpha (0,5 ml = 20 microg) and volume matched saline 0.9% placebo injections. Immediately after the four injections, whilst remaining sitting, the subject was requested to fill out one pain scale (Visual Analogue Scale (VAS)) and to verbally evaluate the pain experience (Verbal Pain Score (VPS)). Finally, the subject was requested to rank the four injections from least to most painful (Treatment Ranking). A total of 42 patients (22 male) participated in the study with a mean age of 56.8 +/- 1.9 years. The average VAS was lower for epoietin-beta (26.8 +/- 4.5 mm) compared to darbepoietin-alpha (58.1 +/- 4.6 mm; p < 0.01). Mean VAS for epoietin-beta did not differ from that of the two placebo saline solutions (0,3 ml 26.3 +/- 4.4 mm; 0,5 ml 18.4 +/- 3.2 mm). Mean VAS for darbepoietin-alpha was significantly higher than placebo (both p < 0.01). Similar observations were obtained for VPS (mean for epoietin-beta 1,3 +/- 0.2 and for darbepoietin-alpha 2.9 +/- 0.2; p < 0.01) and Treatment Ranking (mean for epoietin-beta 2.0 +/- 0.2 and for darbepoietin-alpha 3.2 +/- 0.2; p < 0.01). From the results it can be concluded that subcutaneous epoietin-beta caused statistically significant less pain sensation immediately after injection compared to subcutaneous darbepoietin-alpha . The pain caused by subcutaneous epoietin-beta injection was similar to that caused by placebo control injections whereas subcutaneous darbepoietin-alpha injection was significantly more painful than subcutaneous placebo injections.

Topics: Darbepoetin alfa; Double-Blind Method; Erythropoietin; Female; Hematinics; Humans; Injections, Subcutaneous; Male; Middle Aged; Pain; Recombinant Proteins; Time Factors

To compare injection site pain of subcutaneous (sc) epoetin beta and darbepoetin alfa in adult patients with chronic kidney disease.. This was a multi-centre, randomised, two-arm, single-blind, cross-over study. Patients were randomised to receive weekly sc darbepoetin alfa 30 mug or weekly sc epoetin beta 6000 IU for 2 weeks and were then crossed over to the alternative treatment for 2 weeks. Injection site pain was assessed using a 10 cm ungraduated visual analogue scale (0 = no pain, 10 = worst pain) and a six-point verbal rating scale. Patient preference for treatment was also assessed.. http://clinicaltrials. gov/(NCT00377481).. All randomised patients (N = 48) completed the study. The sample comprised 29 chronic kidney disease patients (Stage 3 or Stage 4), 11 peritoneal dialysis patients and 8 renal transplant patients. Patients perceived significantly less pain with epoetin beta than darbepoetin alfa, using the visual analogue scale (relative pain score = 2.75, darbepoetin alfa:epoetin beta, 95% CI: 1.85, 4.07; p < 0.0001) and the verbal rating scale (median: 0.5, 95% CI: 0.5, 1.0 vs. median: 1.5, 95% CI: 1.0, 2.0; p < 0.0001). Epoetin beta was preferred by significantly more patients (65%) than darbepoetin alfa (10%) (p < 0.001); 25% of patients reported no preference.. Limitations included lack of an epoetin alfa comparator and limited blinding (patients were blinded to treatment, however, an unblinded nurse administered treatment). We show that sc injection of epoetin beta is significantly less painful than darbepoetin alfa and patient preference for epoetin beta confirms that the difference is clinically meaningful.

Topics: Aged; Darbepoetin alfa; Erythropoietin; Female; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Pain; Pain Measurement; Recombinant Proteins

The aim of this study was to compare local pain experienced with subcutaneous (s.c.) injection of epoetin-beta vs. darbepoetin-alpha.. 40 healthy volunteers were enrolled into this single-blind, crossover study. After receiving an injection of placebo, individuals were randomized to receive s.c. injections of epoetin-beta 6,000 IU (0.3 ml) or darbepoetin-alpha 30 mg (0.3 ml), with a 1-week washout period between injections. Local pain was evaluated using a Visual Analog Scale (VAS) and a 6-item Verbal Rating Scale (VRS) immediately after (T0) and 1 h after injection (T1).. The respective mean (standard deviation) and median (range) VAS values at T0 were 1.2 (1.7) and 0.5 (0.0 - 6.9) for epoetin-beta vs. 2.8 (2.4) and 1.9 (0.0 - 9.0) for darbepoetin-alpha (p < 0.0001). At T0, VRS scores demonstrated that 51% of individuals experienced no pain after epoetin- injection compared with 16% of those receiving darbepoetin-alpha. The percentage of individuals perceiving moderate or important pain was significantly greater with darbepoetin-alpha (38%) compared with epoetin-beta (5%, p = 0.0005) and placebo (14%). Pain evaluation at T1 showed no difference between treatment groups. Local tolerance was excellent except for a small hematoma with epoetin- at T1 and with darbepoetin-alpha at T0 which persisted at T1.. In healthy volunteers, s.c. injection of epoetin-beta was significantly less painful than with darbepoetin-alpha and comparable with placebo. No significant pain was apparent at T1 in any group.

Topics: Adolescent; Adult; Cross-Over Studies; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Subcutaneous; Male; Middle Aged; Pain; Pain Measurement; Recombinant Proteins; Single-Blind Method

To determine the cerebrospinal fluid concentrations and the functional and pain outcomes after a single intravenous infusion of erythropoietin at the start of a standard radiotherapy and steroid protocol.. Ten paraparetic patients with malignant extradural spinal cord compression who were eligible for radiotherapy, lumbar puncture and intravenous epoetin alpha were enrolled. The patients received epoetin alpha 1500 IU/kg intravenously over 30 min followed by a standardised dexamethasone and radiotherapy protocol. A lumbar puncture and venipuncture were carried out 24-30 h after the epoetin alpha infusion. The patients were followed closely at defined intervals.. Erythropoietin was detectable in the cerebrospinal fluid in all eight patients sampled (median 92.5 mIU/ml, range 17.8-214.0 mIU/ml). Before treatment, eight patients were non-ambulatory and two patients were ambulatory with assistance. After treatment, eight (80%, 95% confidence interval [CI] 44-97%) improved at least one functional class and recovered or maintained ambulation. Five of seven patients (71%; 95% CI 29-96%) with objective sensory deficits and one of seven (14%; 95% CI 0-58%) catheter-dependent patients recovered. Overall, 78% (95% CI 40-97%) had a pain response.. After an intravenous infusion of epoetin alpha, radiotherapy and steroids, high concentrations of erythropoietin were detectable in the cerebrospinal fluid. Patients with malignant extradural spinal cord compression showed encouraging improvements in neurological function and pain.

Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Dexamethasone; Epoetin Alfa; Erythropoietin; Female; Glucocorticoids; Humans; Infusions, Intravenous; Male; Middle Aged; Pain; Palliative Care; Paraparesis; Recombinant Proteins; Spinal Cord Compression; Spinal Neoplasms; Survival Rate

This study assessed injection site pain following subcutaneous (SC) administration with a continuous erythropoietin receptor activator (C.E.R.A.), compared with darbepoetin alfa in healthy adults.. In a randomized, placebo-controlled, single-centre, single-blind, three-way crossover study, subjects received one of six treatment sequences (ABC/ACB/BAC/BCA/CBA/CAB) involving SC injection of (A) C.E.R.A. 50 microg, (B) darbepoetin alfa 50 microg, or (C) placebo on days 1, 29, and 57. An initial pilot phase (n = 12) was used to determine the sample size for the confirmatory phase (n = 72), and data were combined for the final analysis (n = 84).. The primary endpoint was pain on the 100 mm visual analog scale (VAS) immediately after dosing. Secondary endpoints included VAS at 1 hour after dosing and pain on the six-point verbal rating scale (VRS) immediately and at 1 hour after dosing.. C.E.R.A. was associated with significantly less pain immediately after SC injection compared with darbepoetin alfa: least squares mean VAS 21.5 (95% confidence interval [CI]: 17.5, 25.5) versus 33.4 (95% CI: 28.4, 38.4) (p < 0.0001). Incidence of pain on the VRS was lower with C.E.R.A. compared with darbepoetin alfa immediately after dosing (p < 0.0001). One hour after administration, most subjects had no VRS pain. A study limitation is the small sample size and the findings need to be confirmed in a large trial of chronic kidney disease patients.. SC injection with C.E.R.A. is significantly less painful than SC darbepoetin alfa in healthy adults. Treatment of anemia in chronic kidney disease with SC injection of C.E.R.A. may provide a lower pain burden compared with darbepoetin alfa.

Topics: Adolescent; Adult; Aged; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Subcutaneous; Male; Middle Aged; Pain; Pain Measurement; Placebos; Polyethylene Glycols; Recombinant Proteins

To explore the role of religious belief in coping with disease symptoms and treatment-related side effects in patients with head-and-neck cancer under radiotherapy.. Prospectively collected data were used with a cohort of head-and-neck cancer patients treated by radiotherapy and epoetin beta or placebo within a double-blind multicenter trial. All patients were divided into believers and nonbelievers. Answers to a quality of life questionnaire at four points in time during radiotherapy were analyzed according to both groups. Clinical parameters and therapy side effects were controlled regularly.. 62.1% of the patients (66/105) sent back a baseline questionnaire discriminating between believers and nonbelievers. For 34.2% (40/105) data of all four measures could be obtained. On average, believers felt better in all categories of side effects at all points of time before, during and directly after therapy.. Religious faith seems to play an important role in coping strategies of radiotherapy patients. More research in this area would be worthwhile.

Topics: Adaptation, Psychological; Carcinoma, Squamous Cell; Cohort Studies; Data Interpretation, Statistical; Double-Blind Method; Erythropoietin; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Interviews as Topic; Male; Neoplasm Staging; Pain; Placebos; Prospective Studies; Quality of Life; Radiotherapy; Radiotherapy Dosage; Recombinant Proteins; Religion and Medicine; Spirituality; Surveys and Questionnaires; Time Factors

Darbepoetin-alpha is applicable at longer injection intervals. Our early experience in children on peritoneal dialysis suggested increased injection pain compared to epoetin-beta, possibly due to technical differences or patient anxiety.. To verify a possible difference in the painfulness of the injected fluids per se, we performed a prospective, randomized, double-blind trial in 13 paediatric end-stage renal disease patients. They received three injections of equivalent doses of darbepoetin-alpha or epoetin-beta in 0.6 ml saline, using neutral syringes and 27G needles, at 4 week intervals. Pain perception was recorded immediately and after 30 min on a visual analogue scale (VAS, 0 = no pain, 10 = maximal pain; complemented by 5 faces for young children).. The patients perceived more intense immediate injection pain with darbepoetin-alpha than with epoetin-beta (5.4 +/- 1 vs 2.3 +/- 0.6, P < 0.05). This was confirmed by the impression of the parents (5.3 +/- 1 vs 2.0 +/- 0.9, P < 0.05) and the nurses (4.4 +/- 1 vs 2.2 +/- 0.6, P < 0.05). General injection pain was inversely related to patient age (R = -0.77, P = 0.001). Six patients perceived no or a mild difference in injection pain, whereas 7 subjects reported a markedly higher pain score (> or =4 VAS points) with darbepoetin-alpha. After 30 min, the injection site was largely painless with both drugs. No significant local reactions occurred with either medication (0.3 +/- 0.1 vs 0.3 +/- 0.1 on a 5-score scale).. Subcutaneous injections of darbepoetin-alpha are more painful than those of epoetin-beta in the majority of paediatric patients. The observed difference in painfulness is related to the nature of the injected compounds and may limit the subcutaneous applicability of darbepoetin-alpha in children.

Topics: Adolescent; Adult; Child; Child, Preschool; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Female; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Pain; Prospective Studies; Recombinant Proteins; Renal Dialysis; Severity of Illness Index

To compare the analgesic effects of non nutritive pacifier sucking, oral administration of a 30% saccharose solution, local application of Emla and their association for subcutaneous injection of erythropoietin (EPO) in preterm infants.. Our study was a randomised, prospective study conducted over 5 months. Neonates with a gestational age below 33 weeks of gestation and older than 8 days of life were included if they were treated with EPO (three subcutaneous injections per week during 6 weeks). For each consecutive EPO injection, patients were randomised between four groups of intervention: non nutritive pacifier sucking (T), oral administration of 0.2-0.5 ml of a 30% saccharose solution with non nutritive pacifier sucking (S), local application of Emla with non nutritive pacifier sucking (E), and oral administration of 0.2-0.5 ml of a 30% saccharose solution with local application of Emla and with non nutritive pacifier sucking (S + E). Each child was its own control. Pain was assessed with the Newborn Acute Pain scale (DAN) and with the Neonatal Facial Coding System (NFCS).. Thirty-three neonates were included, representing 265 injections. Distribution was: 41 in group T, 71 in group E, 86 in group S and 67 in group E + S. Mean DAN and NFCS scores were statistically different between groups T, E and S. Analgesic effect of saccharose (-1.05) was greater than Emla (-0.56). Used together, effects were adding up without potentialisation.. This study shows that the association of non nutritive pacifier sucking with oral administration of saccharose and local application of Emla has a better analgesic effect than each of these three interventions alone for subcutaneous injection of EPO.

Topics: Administration, Cutaneous; Administration, Oral; Analysis of Variance; Anesthetics, Combined; Anesthetics, Local; Combined Modality Therapy; Drug Therapy, Combination; Erythropoietin; Facial Expression; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Injections, Subcutaneous; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Pacifiers; Pain; Pain Measurement; Prilocaine; Prospective Studies; Solutions; Sucking Behavior; Sucrose; Treatment Outcome

Patients may complain of pain at the injection site after subcutaneous (s.c.) administration of erythropoietin (EPO). Local pain due to s.c. EPO into the thigh was evaluated in 60 hemodialysis patients in a double-blind, placebo-controlled study. Identical volumes and concentrations (2000 IU in 0.5 ml) of phosphate-buffered epoetin-alpha (EPO-alpha ph), citrate-buffered epoetin-alpha (EPO-alpha ci) and epoetin-beta (EPO-beta) were compared to 0.5 ml of 0.9% saline (SAL), used as placebo. The patients received the 4 injections at the same occasion. For pain evaluation, a verbal scale ranging from no pain (0) to extremely painful (5) and a 10 cm ungraduated visual analogue score (VAS) (0 = no pain, 10 = maximal pain) were used. Treatment acceptance was assessed (yes/no) and expressed as a percentage of the population. Ranking of the preparations from 1 to 4 according to increasing local discomfort was performed. Median verbal pain scores and interquartile ranges were 1.0 (0-2) for SAL, 0.0 (0-2) for EPO-beta, 1.5 (0-3) for EPO-alpha ph (p < or = 0.05 vs SAL and EPO-beta) and 3.0 (2-4) for EPO-alpha ci (p < or = 0.001 vs EPO-alpha ph). VAS was 0.9 (0.5-2.5) for SAL, 0.9 (0.4-2.4) for EPO-beta, 2.7 (0.8-5.7) for EPO-alpha ph (p < or = 0.001 vs SAL and EPO-beta) and 4.2 (1.7-6.4) for EPO-alpha ci (p < or = 0.001 vs EPO-alpha ph). Treatment acceptance was 73% for SAL, 78% for EPO-beta, 60% for EPO-alpha ph (p < or = 0.05 vs EPO-beta) and 32% for EPO-alpha ci (p < or = 0.05 vs EPO-alpha ph). Ranking was 2 (1-3) for SAL, 2 (1-2) for EPO-beta, 3 (1-4) for EPO-alpha ph (p < or = 0.05 vs SAL and EPO-beta) and 4 (3-4) for EPO-alpha ci (p < or = 0.05 vs SAL and EPO-beta) and 4 (3-4) for EPO-alpha ci (p < or = 0.001 vs EPO-alpha ph). In conclusion, s.c. EPO-alpha ph is better accepted than s.c. EPO-alpha ci. However, s.c. EPO-beta is less painful.

Topics: Aged; Anemia; Buffers; Citrates; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Humans; Injections, Subcutaneous; Male; Pain; Pain Measurement; Patient Acceptance of Health Care; Phosphates; Recombinant Proteins; Renal Dialysis

We investigated the efficacy and safety of subcutaneous recombinant human erythropoietin (rHuEpo) in 25 children with chronic renal allograft dysfunction (13 girls, 12 boys, mean age 15.8 +/- 4.2 years) for a treatment period of 9-162 (median 43) weeks. rHuEpo was started once weekly at a dose of 105 +/- 25 U/kg per week in 16 children, twice weekly at a dose of 175 +/- 70 U/kg per week in 6 children, and three times weekly at a dose of 270 +/- 28 U/kg per week in 3 children. The hematocrit increased in 21 children from 23.2% +/- 3.1% to 33% +/- 3.1% within 7.2 +/- 4.9 weeks at a mean rate of 1.98%/week. The hematocrit increase and rHuEpo starting dose were linearly related (delta hematocrit/week = 0.8+0.08 U/kg per week, r = 0.44, P < 0.05). The maintenance dose was 74 +/- 23 (43-114) U/kg per week. Four children failed to reach the target hematocrit, most likely due to noncompliance. Seventeen recurrences of anemia ("anemic episodes") during rHuEpo therapy were identified in 12 children, mostly associated with acute or insidious deteriorations in graft function. There was no acceleration of progression of graft dysfunction with rHuEpo treatment. We conclude that subcutaneous rHuEpo at a single weekly dose of 100 IU/kg per week is highly effective in children with chronic graft dysfunction. Children who appear to be rHuEpo resistant or experience rHuEpo-resistant episodes should be assessed for noncompliance, changes in graft function since the last dosage adjustment, and blood loss, such as seen in dysfunctional uterine bleeding in adolescent girls.

Topics: Adolescent; Adult; Anemia; Blood Pressure; Child; Chronic Disease; Erythropoietin; Female; Graft Rejection; Hematocrit; Humans; Injections, Subcutaneous; Kidney Function Tests; Kidney Transplantation; Male; Pain; Recombinant Proteins

Topics: Adult; Anesthetics, Local; Child; Drug Compounding; Erythropoietin; Female; Humans; Injections, Subcutaneous; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Pain; Prilocaine; Recombinant Proteins; Renal Insufficiency

Subcutaneous injection of citrate-buffered epoetin alpha (EPO-alpha) causes pain. Substitution of citrate buffer with a phosphate buffer in the EPO-alpha resulted in a significant reduction in duration and severity of pain. It is possible that sodium citrate which is present in the EPO-alpha may be the agent that causes discomfort in the patients.

Topics: Adult; Buffers; Citrates; Drug Compounding; Erythropoietin; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Pain; Pain Threshold; Phosphates; Recombinant Proteins; Renal Dialysis; Single-Blind Method; Sodium Citrate

Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given level.. In a randomized, unblinded trial conducted at 24 hemodialysis units at Veterans Affairs medical centers, we assigned 208 patients who were receiving long-term hemodialysis and epoetin therapy to treatment with either subcutaneous or intravenous epoetin. The dose was initially reduced until the hematocrit was below 30 percent and then was gradually increased to a level that would maintain the hematocrit in the range of 30 to 33 percent for 26 weeks. We compared the average doses in the 26-week maintenance phase and the discomfort associated with the two routes of administration.. For the 107 patients treated by the subcutaneous route, the average weekly dose of epoetin during the maintenance phase was 32 percent less than that for the 101 patients treated by the intravenous route (mean [+/-SD], 95.1+/-75.0 vs. 140.3+/-88.5 U per kilogram of body weight per week; P<0.001). Only one patient in the subcutaneous-therapy group withdrew from the study because of pain at the injection site, and 86 percent rated the pain associated with subcutaneous administration as ranging from absent to mild.. In patients receiving hemodialysis, subcutaneous administration of epoetin can maintain the hematocrit in a desired target range, with an average weekly dose of epoetin that is lower than with intravenous administration.

Topics: Algorithms; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Humans; Infusions, Intravenous; Injections, Subcutaneous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Pain; Recombinant Proteins; Renal Dialysis

Study of the antitumour effects of erythropoietin on metastatic renal cell carcinoma.. After giving their informed consent, 20 patients with histologically proven metastatic renal cell carcinoma received subcutaneous recombinant erythropoietin three times a day at a dose of 150 IU/kg when haemoglobin was less than or equal to 12 g/dL or 75 IU/kg when haemoglobin was higher than 12 g/dL. Treatment was continued for a minimum of 8 weeks before reassessment and was continued thereafter, except in the case of progression or excessive toxicity. A staging assessment was performed every 8 weeks and the response was assessed on the basis of WHO criteria. A clinical and laboratory assessment was performed every two months to evaluate toxicity, graded according to the WHO scale. All but one of the patients had received immunotherapy or chemotherapy prior to inclusion in the study.. One complete response (> 12 months), one partial response (8 months), two minor responses, 10 cases of stabilisation and 6 cases of progression were observed. 15 patients received treatment at full doses. In 5 patients, the duration of treatment was reduced before the 8 weeks initially defined because of tumour progression in one patient and because of haemoglobin persistently greater than 15 g/dL in 4 other patients. Adverse effects consisted of 1 case of moderate headache, 2 cases of transient bone pain, and 1 case of transient hypertension.. Erythropoietin exerts a moderate antitumour effect which needs to be confirmed by a phase II trial of first-line treatment in selected patients.

Topics: Aged; Antineoplastic Agents, Hormonal; Bone and Bones; Carcinoma, Renal Cell; Disease Progression; Erythropoietin; Female; Headache; Hemoglobins; Humans; Hypertension; Injections, Subcutaneous; Kidney Neoplasms; Male; Middle Aged; Neoplasm Staging; Pain; Prospective Studies; Recombinant Proteins; Remission Induction; World Health Organization

Recombinant human erythropoietin (rHuEpo) is used to correct anaemia in dialysis patients. Subcutaneous administration of rHuEpo may be associated with pain at the injection site. This study assessed the pain of subcutaneous infiltration of two different preparations of rHuEpo, alpha and beta, and the value of a local anaesthetic (Emla) cream, in reducing the pain of infiltration. Forty-eight haemodialysis patients were enrolled into a double-blind, placebo-controlled, paired-comparison study. Pain was assessed using a visual analogue scale, a verbal descriptive scale and a direct comparison between paired treatments. Subcutaneous injection of rHuEpo alpha was more painful than rHuEpo beta (P < 0.001); using placebo cream 42% of patients described the pain of rHuEpo alpha as severe or very severe, whereas none of the patients found rHuEpo beta so painful. Application of Emla for at least 2 h prior to injection resulted in a significant reduction in the pain of both preparations, but was unable to reduce the pain of rHuEpo alpha to that of rHuEpo beta. Subcutaneous injection of rHuEpo alpha is more painful than rHuEpo beta, even after application of Emla. Although the discomfort of rHuEpo beta is graded as very mild by most adult patients the use of Emla is associated with a significant reduction in discomfort, which may be of benefit to paediatric patients.

Topics: Adult; Aged; Anemia; Anesthetics, Local; Double-Blind Method; Drug Combinations; Erythropoietin; Female; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Middle Aged; Ointments; Pain; Pain Measurement; Prilocaine; Recombinant Proteins; Renal Dialysis

Pain at the injection site with subcutaneous administration of epoetin alfa preparations is a common adverse event, and sometimes precludes self-administration. The pain is caused mainly by the vehicle. The present studies were designed to assess whether pain after subcutaneous administration of the vehicle can be influenced by making the solution iso-osmotic, or by diluting the vehicle by the bacteriostatic agent benzyl alcohol saline (BAS). The volumes injected were 1 ml. We also determined whether reduction of the injected volume of 1 ml to 0.33 ml or to 0.1 ml could be of clinical importance. One millilitre of normal saline served as a placebo control. The studies were done in a double-blind, placebo-controlled, randomized order, cross-over fashion in healthy volunteers. Pain scores were obtained from visual analogue pain scales with no divisions and from 5-point verbal descriptive pain scales. Dilution of the vehicle with BAS resulted in significantly less pain (P < 0.0001) after subcutaneous injection, comparable to levels obtained with normal saline. Making the vehicle iso-osmotic had no effects. Injection of smaller volumes of the vehicle was beneficial with 0.1 ml (P < 0.0001), but the reduction to 0.33 ml was not statistically significant.

Topics: Adult; Benzyl Alcohol; Benzyl Alcohols; Cross-Over Studies; Double-Blind Method; Erythropoietin; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Pain; Pain Measurement; Pharmaceutical Vehicles; Recombinant Proteins; Sodium Chloride

Topics: Adolescent; Child; Child, Preschool; Cross-Over Studies; Erythropoietin; Female; Hematocrit; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Lidocaine; Male; Pain; Peritoneal Dialysis; Recombinant Proteins

The subcutaneous administration of epoetin alfa preparations may cause pain at the injection site. To identify the pain-causing substance in these formulations we performed two double-blind, placebo-controlled, randomized order, cross-over studies. Differences in pain experienced after subcutaneous injection of an epoetin alfa solution and its vehicle were assessed in 36 patients. The vehicle and its component parts, albumin and citrate, were compared in 36 volunteers. Normal saline served as a placebo control in both studies. Pain scores were obtained from visual analogue pain scales with no divisions and from five point verbal descriptive pain scales. Both the epoetin alfa solution and its vehicle caused significantly more pain than normal saline (P < 0.0001) in the patients studied. In volunteers the pain scores with the vehicle or its citrate component were significantly higher (P < 0.0001) when compared with normal saline or with the albumin component of the vehicle. In conclusion, the local pain experienced after subcutaneous administration of epoetin alfa preparations is mainly caused by the citrate component of the buffered solution. Epoetin alfa and the albumin component of the preparation do not play a role in this phenomenon.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Double-Blind Method; Erythropoietin; Female; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Pain; Pain Measurement

Local pain due to subcutaneous erythropoietin (EPO) injection into the thigh was studied using a verbal score ranging from 0 to 4. Equivoluminous doses of epoetin-alpha (Cilag) and epoetin-beta (Boehringer) were compared in 2 controlled single-blind experiments: 10 dialysis patients were treated at random for 4 weeks at consecutive sessions with both brands of EPO, and 40 patients were treated in 1 session only with the 2 brands simultaneously. Pain scores were 1.12 +/- 0.28 versus 0.15 +/- 0.06 (p less than 0.05) and 1.75 +/- 0.19 versus 0.08 +/- 0.04 for epoetin-alpha and epoetin-beta, respectively (p less than 0.001). Treatment acceptance was 48% for epoetin-alpha versus 83% for epoetin-beta (p less than 0.05).

Topics: Aged; Anemia; Erythropoietin; Female; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Pain; Prospective Studies; Recombinant Proteins; Renal Dialysis; Single-Blind Method; Thigh

In this study, we examined the differences in pain score after subcutaneous injection of the epoetin preparations Eprex and Recormon. Patients (n = 30) received 5 injections Eprex and 5 injections Recormon in a randomized double-blind sequence. 10 Min after receiving the injection the patient was asked to complete a visual and a verbal analogue scale and two descriptive scales. The results of 25 patients were used for statistical evaluation. The overall results indicate that there are significantly more patients reporting pain after subcutaneous injection of Eprex than after Recormon (11 versus 2 patients, p less than 0.05; McNemar test). 12 Patients reported no differences in pain. 43 Out of 123 injections Eprex and 69 out of 125 injections Recormon caused no pain (p less than 0.01; chi 2 9.455). For 4 patients Recormon was significantly (p less than 0.05) less painful than Eprex. It can be concluded that Recormon may be a less painful alternative for individual patients reporting pain after subcutaneous injection of Eprex.

Topics: Adult; Aged; Erythropoietin; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Pain

Subcutaneous erythropoietin (SCEPO) is considered to be more effective than intravenously administered erythropoietin. Patient compliance with SC injections will be important in long-term therapy as there have been reports of pain associated with SCEPO. A double-blind randomized study was performed upon 18 ESRD hemodialysis patients receiving regular subcutaneous erythropoietin replacement therapy for treatment of their anemia. The study involved pain assessment by a visual analogue scale VAS and a verbal descriptive scale VDS following 2 subcutaneous injections of preparation A: rhEPO 2000 IU in 1 ml (Cilag), preparation B: rhEPO 2000 IU in 1 ml (Boehringer Mannheim) and 0.9% saline 1 ml (placebo) over a two-week period. The injections were all administered by the same person and replaced the normal EPO injections for the patient during the study period. Results by VAS and VDS based upon 107 responses showed that preparation A was significantly more painful than preparation B (p less than 0.001) or saline (p less than 0.01). An unexpected finding was that preparation B was less painful than the placebo for VAS (p less than 0.05). It seems unlikely that the erythropoietin itself was responsible for the difference. Further work will be necessary to determine the pain causing factor in preparation A, and the possible local anaesthetic factor in preparation B.

Topics: Anemia; Double-Blind Method; Erythropoietin; Female; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Pain; Recombinant Proteins; Renal Dialysis

Topics: Double-Blind Method; Erythropoietin; Humans; Injections, Subcutaneous; Pain; Pain Measurement; Placebos; Renal Dialysis

Topics: Erythropoietin; Humans; Injections, Subcutaneous; Pain

Patients with chronic pain often complain about memory impairments. Experimental studies have shown neuroprotective effects of Carbamylated erythropoietin (Cepo-Fc) in the treatment of cognitive dysfunctions. However, little is currently known about its precise molecular mechanisms in a model of inflammatory pain. Therefore, this study aimed to investigate neuroprotective effects of Cepo-Fc against cognitive impairment induced by the inflammatory model of Complete Freund's Adjuvant (CFA). Carbamylated erythropoietin was administrated Intraperitoneally (i.p) on the day CFA injection, continued for a 21-days period. After conducting the behavioral tests (thermal hyperalgesia and novel object recognition test), western blot and ELISA were further preformed on days 0, 7, and 21. The results of this study indicate that Cepo-Fc can effectively reverse the CFA induced thermal hyperalgesia and recognition memory impairment. Additionally, Cepo-Fc noticeably decreased the hippocampal microglial expression, production of hippocampal IL-1β, and hippocampal apoptosis and necroptosis induced by the inflammatory pain. Therefore, our findings suggest that neuroprotective effects of Cepo-Fc in the treatment of pain related recognition memory impairment may be mediated through reducing hippocampal microglial expression as well as IL-1β production.

Topics: Animals; Disease Models, Animal; Erythropoietin; Freund's Adjuvant; Hippocampus; Hyperalgesia; Male; Memory; Memory Disorders; Microglia; Neuroprotective Agents; Pain; Rats; Recognition, Psychology

Topics: Adult; Anemia, Sickle Cell; Antisickling Agents; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Humans; Hydroxyurea; Hypoxia; Male; Middle Aged; Oxygen Inhalation Therapy; Pain; Reticulocyte Count; Retrospective Studies; Sleep Disorders, Intrinsic; Treatment Outcome; Young Adult

this study was designed to examine the neuroprotective effects of asialo-erythropoietin (A-EPO) in a rat model of lumbar disc herniation.. to investigate the effects of A-EPO on pain-related behavior, the expression of phosphorylated-p38 (p-p38) mitogen activated kinase, and the expression of tumor necrosis factor alpha (TNF-α) induced by nucleus pulposus (NP) application on the nerve root.. erythropoietin (EPO) has neuroprotective effects in a variety of models of central and peripheral nerve injuries. However, EPO is a hematopoietic growth factor and can therefore cause significant side effects such as thicker blood and promotion of blood clotting. A-EPO is a neuroprotective derivative of EPO that is not hematopoietic.. female Sprague-Dawley rats (n = 149) were used in this study. NP harvested from the tail was applied to the left L5 nerve root and the rats were then divided into four groups: NP + nontreatment group, no further treatment; NP + A-EPO group, 13.4 microg/kg A-EPO; NP + EPO group, 13.4 microg/kg EPO; and NP + vehicle group, received vehicle. The substances were administered subcutaneously 1 day before surgery and daily for 2 weeks. In the sham group of animals, the L5 nerve root was exposed and NP was not applied. Withdrawal thresholds were determined by the von-Frey test 28 days after surgery. The expressions of p-p38 and TNF-α were assessed by immunohistochemical and immunoblotting analysis. Data were analyzed by unpaired Student t test and Dunnett t test (significance level, P < 0.05).. in the NP + nontreatment and NP + vehicle groups, withdrawal thresholds were decreased significantly for 28 days compared with the sham group (P < 0.05). In the NP + A-EPO group, the thresholds were significantly increased on day 28, and in the NP + EPO group, the thresholds were significantly increased on days 21 and 28 (P < 0.05) compared with the NP + nontreatment and NP + vehicle groups. The expression of p-p38 in the NP + A-EPO group was significantly lower than that in the NP + vehicle group on day 1 (P < 0.05). The expression of TNF in the NP + A-EPO and NP + EPO groups was significantly lower than that in the NP + vehicle group on days 1 and 7 (P < 0.05).. A-EPO improved pain-related behavior and reduced the expression of p-p38 and TNF-α. The effect of A-EPO may be related to the inhibitory action of p-p38 and TNF-α in the dorsal root ganglion.

Topics: Animals; Asialoglycoproteins; Behavior, Animal; Erythropoietin; Female; Ganglia, Spinal; Immunoblotting; Immunohistochemistry; Intervertebral Disc; Intervertebral Disc Displacement; p38 Mitogen-Activated Protein Kinases; Pain; Pain Threshold; Rats; Rats, Sprague-Dawley; Transplantation, Autologous; Tumor Necrosis Factor-alpha

Painful stimuli during neonatal stage may affect brain development and contribute to abnormal behaviors in adulthood. Very few specific therapies are available for this developmental disorder. A better understanding of the mechanisms and consequences of painful stimuli during the neonatal period is essential for the development of effective therapies. In this study, we examined brain reactions in a neonatal rat model of peripheral inflammatory pain. We focused on the inflammatory insult-induced brain responses and delayed changes in behavior and pain sensation. Postnatal day 3 pups received formalin injections into the paws once a day for 3 days. The insult induced dysregulation of several inflammatory factors in the brain and caused selective neuronal cell death in the cortex, hippocampus and hypothalamus. On postnatal day 21, rats that received the inflammatory nociceptive insult exhibited increased local cerebral blood flow in the somatosensory cortex, hyperalgesia, and decreased exploratory behaviors. Based on these observations, we tested recombinant human erythropoietin (rhEPO) as a potential treatment to prevent the inflammatory pain-induced changes. rhEPO treatment (5,000 U/kg/day, i.p.), coupled to formalin injections, ameliorated neuronal cell death and normalized the inflammatory response. Rats that received formalin plus rhEPO exhibited normal levels of cerebral blood flow, pain sensitivity and exploratory behavior. Treatment with rhEPO also restored normal brain and body weights that were reduced in the formalin group. These data suggest that severe inflammatory pain has adverse effects on brain development and rhEPO may be a possible therapy for the prevention and treatment of this developmental disorder.

Topics: Animals; Animals, Newborn; Behavior, Animal; Body Weight; Brain; Cell Death; Cerebrovascular Circulation; Cytokines; Disease Models, Animal; Erythropoietin; Exploratory Behavior; Formaldehyde; Humans; Hyperalgesia; Inflammation; Inflammation Mediators; Neurons; Neuroprotective Agents; Organ Size; Pain; Rats

The aim of study was to analyze the results of anemia treatment with darbepoetin alfa and erythropoietin beta in patients with chronic kidney disease (3-5 stage of CKD) in predialysis period.. In the study the results of anemia treatment with darbepoetin alfa and erythropoietin beta were analyzed in respectively 35 and 20 patients during 11 months, and its influence on blood pressure and the rate of progression of chronic kidney disease. After 2 months of darbepoetin alfa treatment 10 mg/month and after 4 months of darbepoetin alfa treatment 20 mg/month the hemoglobin target serum levels in male and female patients were reached. In 3 patients the hemoglobin serum level was increased over 13 g/dl and was stable up to the end of treatment. During 11 months observation the value of blood pressure was not changed. Similarly, a creatinine serum level was stable in females but increased in males. Therapy with darbepoetin alfa was well tolerated, however some patients were complained for subcutaneous injection pain.. After erythropoietin beta treatment 2000 IU/week the hemoglobin target level in serum was achieved in 3 females after 9 months and 7 males after 6 months. In 3 patients, in one male after 6 months and two females after 8 months the hemoglobin serum levels were increased over 13 g/dl and was stable up to the end of treatment.. During 11 months of observation blood pressure was not changed but a creatinine serum level was increased in females and in males. Erythropoietin beta was well tolerated and injection pain was smaller compared to darbepoetin alfa.

Topics: Anemia; Blood Pressure; Chronic Disease; Creatinine; Darbepoetin alfa; Disease Progression; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Diseases; Male; Middle Aged; Pain; Treatment Outcome

Circulating endothelial progenitor cells (EPCs) counts were determined in patients with sickle cell disease (SCD) to elucidate their role in SCD-related ischemia-induced angiogenesis and reendothelialization.. Circulating EPC counts (KDR(+)/CD34(+)/Cd45(dim) cells) and their relation to serum levels of EPC mobilizing growth factors erythropoietin, vascular endothelial growth factor, and interleukin-8 were investigated in SCD patients during asymptomatic state (n=66) and painful crisis (n=36) and compared to healthy controls (n=13).. EPC counts were comparable between controls (0; range, 0-1.1 cells/mL) and patients (0; range, 0-0 cells/mL) in asymptomatic state, but were significantly higher during painful crisis (41.7; range, 0-186 cells/mL; p<0.05). Also in a paired analysis of 12 patients who were included both during asymptomatic state and painful crisis, EPC counts increased significantly during painful crisis (from 0 [range, 0-0] to 26 [range, 0-149 cell/mL; p<0.05). EPC counts were not related to any of the measured growth factors.. The higher EPC counts during painful crisis might indicate a role for EPC mobilization in reendothelialization. As a relationship of EPCs with the established mobilizing growth factors, measured in this study was not observed, the mechanism of EPC mobilization in SCD remains to be elucidated.

Topics: Adult; Anemia, Sickle Cell; Endothelial Cells; Erythropoietin; Female; Humans; Interleukin-8; Ischemia; Leukocyte Count; Male; Neovascularization, Pathologic; Pain; Stem Cells; Vascular Endothelial Growth Factor A

Topics: Anemia; Diphosphonates; Erythropoietin; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Osteolysis; Pain; Paraneoplastic Syndromes; Recombinant Proteins

Erythropoietin (Epo) has been shown to have potent anti-apoptotic activity in central nervous system neurons in animal models of ischaemic injury. Recently, Epo and its receptor (EpoR) have been identified in the peripheral nervous system [Campana & Myers (2001), FASEB J., 15, 1804-1806]. Herein, we demonstrate that in painful neuropathy caused by L5 spinal nerve crush (SNC), therapy with recombinant human Epo (rhEpo) reduced dorsal root ganglion (DRG) apoptosis and pain behaviours. Quantification of both DRG neurons and satellite cells revealed that vehicle-treated, crush-injured DRGs had 35.5 +/- 8.3% apoptotic neurons and 23.5 +/- 2.36% satellite cells compared with 7.5 +/- 6.3% apoptotic neurons and 6.4 +/- 3.94% satellite cells in rhEpo-treated, crush-injured DRGs (P < 0.05). While rhEpo-treated animals were not initially protected from mechanical allodynia associated with L5 SNC, rhEpo did significantly improve recovery rates compared to vehicle-treated animals (P < 0.01). Systemic rhEpo therapy increased JAK2 phosphorylation, a key anti-apoptotic signalling molecule for Epo-induced neuroprotection, in DRGs after crush. Dual immunofluorescence demonstrated Epo-induced JAK2-p was associated with both neuronal and glial cells. JAK2-p was associated with NF200-positive large neurons and with smaller neurons. This population of small neurons did not colocalize with IB4, a marker of nonpeptidergic, glial derived growth factor-responsive neurons. The findings link anti-apoptosis activities of Epo/EpoR/JAK2 in DRG neurons capable of inducing protracted pain states with reductions in pain behaviours, and therefore support a role for Epo therapy in the treatment of neuropathic pain.

Topics: Animals; Apoptosis; Behavior, Animal; Blotting, Western; Carbocyanines; Cell Count; Disease Models, Animal; Dose-Response Relationship, Drug; Erythropoietin; Female; Fluorescent Antibody Technique; Functional Laterality; Ganglia, Spinal; Glial Fibrillary Acidic Protein; Humans; Hyperalgesia; In Situ Nick-End Labeling; Janus Kinase 2; Microscopy, Confocal; Neurofilament Proteins; Pain; Pain Measurement; Pain Threshold; Peripheral Nervous System Diseases; Plant Lectins; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Rats; Rats, Sprague-Dawley; Ribosome Inactivating Proteins; Satellite Cells, Perineuronal; Time Factors

The authors investigated the association of L5 proximal nerve root injury with spinal cord neuronal apoptosis (histologic) and whether exogenous erythropoietin therapy might reduce apoptosis/or pain (behavioral).. The first objective was to determine whether nerve root crush induces specific programmed cell death of spinal neurons in the dorsal and ventral horn and whether this is correlated with pain behaviors. The second objective was to determine if exogenous erythropoietin might reduce apoptosis and/or pain.. Whether spinal neuronal apoptosis is correlated with pain behaviors following nerve root injury remains unknown. It has been hypothesized that neuroprotective factors may alleviate pain behaviors by protecting neurons from death. Erythropoietin is a hematopoietic growth factor that recently has been demonstrated as a potent neuroprotective factor against ischemic damage in the brain. The effects of erythropoietin on pain and spinal cord neurons have not been examined.. Sprague-Dawley rats received a L5 proximal nerve root crush injury or sham operation and were separated into two treatment groups for subcutaneous injection: 1) vehicle; 2) recombinant human erythropoietin, 2680 U/kg. The rats were sacrificed, and spinal cords were removed for apoptotic and immunohistochemical analysis at 0, 1, and 3 days after surgery. To determine whether recombinant human erythropoietin prevented mechanical allodynia in animals with nerve root crushes (n = 12/group), both treatment groups were tested for pain behaviors using the von Frey test at -1, -2, -3, 1, 3, 7, 11, and 14 days after surgery.. After nerve root injury, apoptotic neurons increased by 80% in the ipsilateral spinal cord and moderately in contralateral spinal cord in vehicle-treated animals compared to uninjured controls. Recombinant human erythropoietin reduced (P < 0.05) neuronal apoptosis in both superficial dorsal and ventral horns of the spinal cord. This corresponded with identification of erythropoietin and its receptors on spinal neurons and reductions in TNF-alpha colocalization in ventral horn neurons. Mechanical allodynia developed in the corresponding ipsilateral hind paw within 1 day and was sustained until day 14. Recombinant human erythropoietin-treated animals demonstrated faster recovery from mechanical allodynia compared with vehicle-treated controls (P < 0.05).. Our findings indicated that L5 proximal nerve root crush increased neuronal apoptosis in the superficial dorsal and ventral horn that correlated with mechanical allodynia. Exogenous recombinant human erythropoietin facilitated receptor-mediated neuroprotection of spinal cord neurons and faster recovery from mechanical allodynia. Erythropoietin may be a potential therapeutic factor for patients with low back pain by providing pain relief and neuroprotection.

Topics: Animals; Anterior Horn Cells; Apoptosis; Behavior, Animal; Erythropoietin; Female; Nerve Crush; Neuroprotective Agents; Pain; Posterior Horn Cells; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Spinal Cord; Spinal Nerve Roots; Trauma, Nervous System; Tumor Necrosis Factor-alpha

Topics: Anemia, Sickle Cell; Antisickling Agents; Erythropoietin; Female; Hemoglobins; Humans; Hydroxyurea; Pain

Topics: Adult; Anemia, Sickle Cell; Cell Adhesion; Chronic Disease; Endothelium, Vascular; Erythrocytes; Erythropoietin; Female; Hemoglobins; Humans; Hydroxyurea; Microcirculation; Pain; Pain Management

Topics: Erythropoietin; Humans; Injections, Subcutaneous; Pain

Topics: Dose-Response Relationship, Drug; Erythropoietin; Humans; Infusions, Intravenous; Injections, Subcutaneous; Pain; Patient Acceptance of Health Care; Recombinant Proteins

Topics: Erythropoietin; Gout; Humans; Male; Middle Aged; Pain; Syndrome; Toes; Vasculitis

Topics: Anemia, Sickle Cell; Erythrocyte Deformability; Erythrocytes; Erythropoietin; Hematocrit; Hemoglobins; Humans; Infarction; Oxygen; Pain