Ambulatory Pain Research Articles

Regulation of spinal neuroimmune responses by prolonged morphine treatment in a rat model of cancer induced bone pain

Cancer induced bone pain (CIBP) is a major clinical problem. Although opioids remain the principal axis in drug therapies for CIBP, their sustained application is known to induce cellular and molecular adaptations including enhanced neuroimmune reactivity. This is generally characterized by glial activation and proinflammatory cytokine production which frequently results in pharmacological tolerance. This research was performed to investigate spinal neuroimmune responses after prolonged systemic morphine treatment in a rat model of CIBP. The model was established using a unilateral intra-tibia injection of Walker 256 mammary gland carcinoma cells. Subcutaneous morphine was repeatedly administered from postoperative days 14 to 19. Mechanical allodynia to von Frey filaments and ambulatory pain scores were recorded to investigate changes of nociceptive behaviors. Spinal glial activation was detected by immunohistochemistry and real-time PCR; the production of proinflammatory cytokines (IL-1β and TNF-α) was examined through real-time PCR and ELISA. Results showed that chronic morphine use failed to elicit analgesic tolerance in the rat CIBP model. Moreover, the treatment had no significant influence on the activated spinal glia morphology, cell density and expression of special cytomembrane markers, whereas it significantly down-regulated the local proinflammatory cytokine production at the mRNA and protein level. Collectively, these data suggest that chronic morphine treatment in CIBP is not concomitant with pharmacological tolerance, at least partially because the treatment fails to amplify spinal neuroimmune responses.

A new transmucosal drug delivery system for patients with breakthrough cancer pain: the fentanyl effervescent buccal tablet

Breakthrough pain, a transitory severe pain with the background of otherwise controlled persistent pain has a prevalence between 52% and 67% in outpatients with cancer. Medications for such sudden-onset pain require non-invasive delivery of a potent and short-acting opioid for rapid pain relief. Although oral transmucosal delivery of fentanyl citrate (OTFC) has been shown to provide better pain relief than a typical oral opioid administration such as morphine sulfate immediate release (MSIR) in the management of breakthrough pain in patients with cancer-related pain, newer delivery systems offer a potential for further enhancement of pain relief. The fentanyl effervescent buccal tablet (FBT) formulation employs a novel drug delivery system that relies on an effervescence reaction to improve buccal fentanyl absorption. Using the effervescence reaction results in the production and dissipation of carbon dioxide with a dynamic shift in pH as the tablet dissolves. The induced low pH favors dissolution of fentanyl citrate in saliva (higher water solubility). The subsequent increase in pH thereafter favors the buccal absorption of non-ionized fentanyl across the buccal mucosa. Such a pH "pumping" mechanism increases the permeation of fentanyl into and through the buccal to the vascular system from where the agent is transported to the specific opioid receptor sites in the CNS. Compared with OTFC, data in healthy volunteers show that the effervescence reaction employed in FBT increases the total amount and the speed of absorption of fentanyl being absorbed. Compared with OTFC there is an increase in peak fentanyl blood concentrations, and an enhancement of the amount of buccal delivery of fentanyl. Such favorable data are underlined by the results of clinical studies where the FBT technology was studied in patients with breakthrough pain in chronic malignant pathologies.

A randomized, double-blind, prospective study comparing the efficacy of continuous versus pulsed radiofrequency in the treatment of lumbar facet syndrome

Study Objectives To compare the efficacy of continuous radiofrequency (CRF) thermocoagulation with pulsed radiofrequency (PRF) in the treatment of lumbar facet syndrome. Design Prospective, randomized, double-blinded study. Setting Ambulatory pain clinic at a level-I trauma center and teaching institution. Patients 50 ASA physical status I, II, and III patients, at least 18 years of age, scheduled to undergo CRF or PRF for lumbar back pain. Interventions Target facet joints were identified with oblique radiographic views. Continuous radiofrequency thermocoagulation was delivered at 80°C for 75 seconds, while PRF was delivered at 42°C with a pulse duration of 20 ms and pulse rate of two Hz for 120 seconds. Measurements Visual analog scale (VAS) pain assessment and Oswestry Low Back Pain and Disability Questionnaire (OSW) were administered at baseline and then at three months. Comparisons between groups and within groups were made of the relative percentage improvement in VAS and OSW scores. Main Results No significant differences in the relative percentage improvement were noted between groups in either VAS ( P = 0.46) or OSW scores ( P = 0.35). Within the PRF group, comparisons of the relative change over time for both VAS ( P = 0.21) and OSW scores ( P = 0.61) were not significant. However, within the CRF group, VAS ( P = 0.02) and OSW scores ( P = 0.03) showed significant improvement. Conclusions Although there was no significant difference between CRF and PRF therapy in long-term outcome in the treatment of lumbar facet syndrome, there was a greater improvement over time noted within the CRF group.

Current and Emerging Treatments for Mild/Moderate Acute Ambulatory Pain

Nonsteroidal anti-inflammatory drugs (NSAIDs), the mainstay of therapy for acute musculoskeletal pain, are among the most widely used drugs in the world. The major limitation of traditional (nonselective) NSAIDs is gastrointestinal (GI) toxicity, which includes dyspepsia, mucosal injury, and serious events, such as ulcers, GI bleeding, and perforation. This article reviews the mechanism of action, safety, and efficacy of traditional and selective NSAIDs (coxibs); risk factors for GI complications; and strategies for reducing risk and preventing NSAID-related gastropathy and cardiovascular complications. The article also discusses the use of aspirin for cardioprotection in patients taking analgesic/anti-inflammatory agents for musculoskeletal pain and the need to balance competing GI and cardiovascular risks. Topical NSAIDs and other formulations that may prove to be safer than currently available agents also are addressed.

Pharmacokinetic and pharmacodynamic properties of tramadol IR and SR in elderly patients: A prospective, age-group-controlled study

Background: Tramadol is widely prescribed, even to the eldest patients. Although age-related differences in pharmacologic responsiveness are to be expected, the pharmacodynamic and pharmacokinetic (PK) properties of tramadol have not been systematically compared between patients of various ages. Objective: The aim of this study was to explore the effectiveness, PK properties, and safety profile of 2 galenic tramadol formulations in 3 similarly sized age groups with malignant and nonmalignant pain of moderate to severe intensity. Methods: This prospective, age-group-controlled study was conducted at the ambulatory pain clinic of the Landeskrankenhaus Kärnten, Klagenfurt, Austria. Male and female adults with malignant and nonmalignant pain of moderate to severe intensity were eligible. Patients were stratified into similarly sized age groups, as follows: ≥75, 65-<75, and <65 years. Patients first received the immediate-release galenic formulation of tramadol (tramadol IR) until steady state was achieved, followed by the sustained-release formulation (tramadol SR) until steady state. Serum concentrations of tramadol and its active metabolite (O-desmethyl-tramadol [M1]) were measured using gas chromatography to estimate the age-related PK handling of the analgesic drug. Three validated scales were used to measure pain intensity during the study: a 100-mm visual analog scale (VAS), an 11-point numeric analog scale (NAS), and a 4-point verbal rating scale (VRS). Tolerability was assessed by evaluating daily answers about the potential occurrence of adverse events (and respective details such as type and severity) from baseline until the end of the observation period. Results: A total of 100 patients were enrolled (58 women, 42 men; mean [SD] age, 65.2 [15.0] years; ≥75, 30 patients; 65-<75, 31 patients; and <65 years, 39 patients). Predominant causes of pain were neoplasms (27.4% of causes) and injury and other external causes (20.8%), and diseases of the musculoskeletal and connective-tissues systems (19.8%). Fifty-five patients completed the study and provided all data as planned. Mean (SEM) steady-state tramadol IR doses were 250 (20.2), 277 (39.8), and 325 (33.1) mg/d in patients aged ≥75, 65-<75, and 65 years, respectively ( P = NS); tramadol SR, 278 (27.5), 306 (39.7), and 340 (35.1) mg/d ( P = NS). Serum concentrations of tramadol and M1 were statistically similar across all 3 age groups. Overall, mean pain intensity scores, as measured using the VAS and NAS, were decreased from baseline (62.4 [2.0] mm and 6.22 [0.22] points, respectively) to steady state with tramadol IR (23.6 [2.9] mm and 2.65 [0.30] points) and tramadol SR (16.9 [2.5] mm and 1.91 [0.26] points) (all, P < 0.001). Pain intensity before and improvements during both treatment phases were similar across all 3 age groups. Results: for pain intensity on the VRS also did not find age-related differences. The predominant adverse effects were nausea (27.0% of patients), dizziness and giddiness (18.0%), and malaise and fatigue (15.0%); no significant differences in adverse events were found between age groups. Conclusions: The fate of tramadol and its active metabolite, and their clinical effects, have been examined here for the first time in a prospective cohort study, which compared patients aged <65 years, 65-<75 years, and ≥75 years. In contrast to expecta tions, it was concluded that tramadol IR and tramadol SR were both generally well tolerated and effective in the treatment of moderate to severe pain in any of the 3 age groups in these patients. Although the eldest group of patients consumed, on average, 20% less tramadol ( P = NS) than the youngest group, the PK properties of both drugs were not changed when given to elderly patients.

Case report: Overnight Hospital Stay for Minimally Invasive Bilateral Total hip Arthroplasty

Bilateral total hip arthroplasty was performed on a 58-year-old man. He was successfully discharged home from hospital the following morning, 23 hours post surgery. A direct anterior, minimally invasive approach was used which avoided detachment of hip musculature. Preoperative assessment was carried out, with early multidisciplinary team input. Modified anaesthetic techniques with an ambulatory pain pump were employed. Follow-up in the community was carried out by an outreach team. All these factors were important in a successful early supported discharge. We believe this to be the first such case reported.

A rat model of bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells

This study described a modified rat model of bone cancer pain. Syngeneic Walker 256 mammary gland carcinoma cells were injected into the tibia medullary cavity via intercondylar eminence. Series of tests were carried out including bone radiology, bone histology, ambulatory pain, thermal hyperalgesia, mechanical allodynia, weight bearing ability, and electrophysiological recording from primary afferent fibers. The rats inoculated with carcinoma cells showed significant ambulatory pain, mechanical allodynia, and reduction in weight bearing, as well as increased incidence of spontaneous activity in Aβ fibers in affected limb, whereas PBS (vehicle) or heat-killed cells (sham) injected rats showed no significant difference in comparison to normal rats. The pain hypersensitive behaviors were aggravated with time and destruction of bone. Interestingly, mechanical allodynia was also observed in the contralateral limb, indicating the involvement of ‘mirror image’ pain in bone cancer pain. In summary, the present study provided a useful and easily established rat model of bone cancer pain which will contribute to further study of the mechanisms underlying cancer pain.

Case report: Overnight hospital stay for minimally invasive bilateral total hip arthroplasty

Bilateral total hip arthroplasty was performed on a 58-year-old man. He was successfully discharged home from hospital the following morning, 23 hours post surgery. A direct anterior, minimally invasive approach was used which avoided detachment of hip musculature. Preoperative assessment was carried out, with early multidisciplinary team input. Modified anaesthetic techniques with an ambulatory pain pump were employed. Follow-up in the community was carried out by an outreach team. All these factors were important in a successful early supported discharge. We believe this to be the first such case reported.

Use of a Regional Infusion Pump to Control Postoperative Pain After an Abdominoplasty

This study presents the clinical results for 20 patients who underwent abdominoplasty. A subset of these patients were given a pain relief system that provides continuous infusion of a nonnarcotic medication directly into the surgical wound to reduce postoperative pain. Whereas patients received a pain pump in addition to standard oral/intramuscular pain medication, 10 patients received only the standard oral and intramuscular postoperative pain medications. All 20 patients then were asked to complete an evaluation of their postoperative discomfort and pain. The findings show a significant reduction in postoperative pain with the use of the ambulatory pain pump. The simplicity of installing and running the pump and the benefits obtained, including early ambulation and less pain as well as reduced need and strength of narcotic medications lead the authors to believe that the implementation of this pain control technology soon will become widespread in their specialty. The study indicates that patients require less sedation and get out of bed sooner with this device, thereby reducing the incidence of deep venous thrombosis, pulmonary emboli, and narcotic-dependency.

Ambulatory monitoring of physical activity and symptoms in fibromyalgia and chronic fatigue syndrome

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are associated with substantial physical disability. Determinants of self-reported physical disability are poorly understood. This investigation uses objective ambulatory activity monitoring to compare patients with FM and/or CFS with controls, and examines associations of ambulatory activity levels with both physical function and symptoms during activities of daily life. Patients with FM and/or CFS (n = 38, mean +/- SD age 41.5 +/- 8.2 years, 74% women) completed a 5-day program of ambulatory monitoring of physical activity and symptoms (pain, fatigue, and distress) and results were compared with those in age-matched controls (n = 27, mean +/- SD age 38.0 +/- 8.6 years, 44% women). Activity levels were assessed continuously, ambulatory symptoms were determined using electronically time-stamped recordings at 5 time points during each day, and physical function was measured with the 36-item Short Form health survey at the end of the 5-day monitoring period. Patients had significantly lower peak activity levels than controls (mean +/- SEM 8,654 +/- 527 versus 12,913 +/- 1,462 units; P = 0.003) and spent less time in high-level activities when compared with controls (P = 0.001). In contrast, patients had similar average activity levels as those of controls (mean +/- SEM 1,525 +/- 63 versus 1,602 +/- 89; P = 0.47). Among patients, low activity levels were associated with worse self-reported physical function over the preceding month. Activity levels were inversely related to concurrent ambulatory pain (P = 0.031) and fatigue (P < 0.001). Pain and fatigue were associated with reduced subsequent ambulatory activity levels, whereas activity levels were not predictive of subsequent symptoms. Patients with FM and/or CFS engaged in less high-intensity physical activities than that recorded for sedentary control subjects. This reduced peak activity was correlated with measures of poor physical function. The observed associations may be relevant to the design of behavioral activation programs, because activity levels appear to be contingent on, rather than predictive of, symptoms.

213. Peripherally Delivered Glutamic Acid Decarboxylase (GAD) Gene Therapy for Below-Level Spinal Cord Injury Neuropathic Pain

Top of pageAbstract Pain associated with cancer in bone is a common clinical problem that is often difficult to treat using conventional therapies. Previously we demonstrated that transduction of dorsal root ganglia (DRG) by subcutaneous inoculation of non-replicating herpes simplex virus (HSV) vectors expressing the inhibitory neurotransmitter proenkephalin (vector SHPE) or the anti-inflammatory peptides interleukin-4 (vector S4IL4) or tumor necrosis factor alpha soluble receptor (vector T0TNFSR) administered separately reduce pain-related behavior in a mouse model of bone cancer. SHPE acts through activation of inhibitory (opioid) receptors at the spinal level. S4IL4 and T0TNFSR act through reduction of the spinal inflammatory response characteristic of chronic pain. Since these vectors act through separate mechanisms we tested the hypothesis that combined therapy would be more effective than any single vector alone. Male C3H/HeJ mice were injected with 105 NTCT 2472 osteolytic sarcoma cells into the medullary space of the right femur. One week later the ipsilateral lumbar DRG were transduced by subcutaneous inoculation into the plantar surface of the foot with 20 ul containing SHPE and S4IL4 (5 × 106 pfu each) or 20 ul containing SHPE, S4IL4, and T0TNFSR (3.3 × 106 pfu each). Pain behavior was assessed 1 and 2 weeks after vector inoculation using a 4-point spontaneous ambulatory pain score (SAPS) and mechanical allodynia (MA). These results were compared to similarly treated mice that received 10 ul containing 1 × 107 pfu of each vector separately and to mice that received 1 × 107 pfu of the control vector QOZHG. Tumor-bearing mice inoculated with all three vectors together demonstrated reduced SAPS and MA compared to single vector inoculated mice. These results suggest that therapies designed to affect different physiological pathways associated with bone cancer pain may be more efficacious than single agents and demonstrate the feasibility of using HSV based gene therapy in the treatment of chronic pain.

Risk Assessment of Hemorrhagic Complications Associated With Nonsteroidal Anti-inflammatory Medications in Ambulatory Pain Clinic Patients Undergoing Epidural Steroid Injection

Risk Assessment of Hemorrhagic Complications Associated With Nonsteroidal Anti-inflammatory Medications in Ambulatory Pain Clinic Patients Undergoing Epidural Steroid Injection

Risk assessment of hemorrhagic complications associated with nonsteroidal antiinflammatory medications in ambulatory pain clinic patients undergoing epidural steroid injection.

We prospectively studied 1035 individuals undergoing 1214 epidural steroid injections to determine the risk of hemorrhagic complications. A history of bruising or bleeding was present in 176 (15%) patients. A platelet count was assessed in 77 patients before the epidural steroid injection; none was less than 100 x 10(9)/L. Nonsteroidal antiinflammatory drugs (NSAIDs) were reported by 383 (32%) patients, including 34 patients on multiple medications. Aspirin was the most common NSAID and was noted by 158 patients, including 104 patients on 325 mg or less per day. There were no spinal hematomas (major hemorrhagic complications). Blood was noted during needle or catheter placement in 63 (5.2%) patients (minor hemorrhagic complications). NSAIDs did not increase the frequency of minor hemorrhagic complications. However, increased age, needle gauge, needle approach, needle insertion at multiple interspaces, number of needle passes, volume of injectant, and accidental dural puncture were all significant risk factors for minor hemorrhagic complications. There were 42 patients with new neurologic symptoms or worsening of preexisting complaints that persisted more than 24 h after injection; median duration of the symptoms was 3 days (range, 1-20 days). Our results confirm those of previous studies performed in obstetric and surgical populations that document the safety of neuraxial techniques in patients receiving NSAIDs. We conclude that epidural steroid injection is safe in patients receiving aspirin-like antiplatelet medications. Minor worsening of neurologic function may occur after epidural steroid injection and must be differentiated from etiologies requiring intervention. Previous studies performed in obstetric and surgical populations have demonstrated that antiplatelet therapy does not increase the risk of spinal hematoma associated with spinal or epidural anesthesia and analgesia. We confirm the safety of epidural steroid injection in patients receiving aspirin-like medications.

Percutaneous Electrical Nerve Stimulation for Low Back Pain: A Randomized Crossover Study

GHONAME, EL-SAYED A.; CRAIG, WILLIAM F.; WHITE, PAUL F.; AHMED, HESHAM E.; HAMZA, MOHAMED A.; HENDERSON, BRENT N.; GAJRAJ, NOOR M.; HUBER, PHILIP J.; GATCHEL, ROBERT J. Author Information

Long-term epidural analgesia for pregnancy-induced intercostal neuralgia

Intercostal neuralgia is one of many possible neurological disorders associated with pregnancy. A woman presented in the 34th week of her 4th pregnancy with progressing right-sided pain and hypoesthesia in the ribs, right upper quadrant of the abdomen, and mid-thoracic area of her back. With a clinical diagnosis of pregnancy-related intercostal neuralgia, we inserted an epidural catheter at T8 for ambulatory pain management. A continuous infusion of bupivacaine was titrated by concentration and rate until adequate analgesia was obtained. The final effective dose consisted of 0.125% bupivacaine at 6 ml/h with a patient-controlled bolus dose of 2 ml every 30 min as needed (4–6 boluses per 24-h period). This allowed the patient to continue to work full-time and perform daily activities with minimal discomfort. The epidural infusion was continued until the patient went into spontaneous labor 28 days after the initial clinical visit. A full-term infant was delivered without incident. No major complications occurred such as local anesthetic toxicity, hypotension, motor weakness, or infection. Minor complications included disconnection of the catheter cap and accidental dislodgment, which required placement of a second epidural catheter. For this patient, an appropriately placed chronic epidural catheter and a titrated continuous infusion of bupivacaine provided adequate and safe analgesia for pregnancy-associated intercostal neuralgia.

Assessment of long term treatment outcome of an ambulatory pain clinic

Assessment of long term treatment outcome of an ambulatory pain clinic

Outpatient treatment of patients with chronic pain: an analysis of cost savings.

To control costs, the University of Tennessee Center for Pain Management added an ambulatory pain rehabilitation program to its existing inpatient hospitalization program. The impact of this program was assessed by comparing the first 25 patients treated in 1985 (prior to the introduction of outpatient management) with the first 25 patients treated in 1987 (after outpatient management was established). Twenty of the 25 patients seen in 1985 required hospitalization, while in 1987 nine patients were hospitalized and 10 patients were placed in outpatient rehabilitation. The total cost for treating 25 patients in 1985 was $571,200 but decreased to $191,000 in 1987. Hospital charges were the greatest single cost factor in 1985 ($321,500) but were only $61,000 in 1987. Success rates as measured by a return to previous employment were not significantly changed (13 of 25 returned to work in 1985, and 11 of 25 returned to work in 1987).

化膿性股関節炎による思春期股関節症に対する筋解離術の経験

Two cases of adolescent osteoarthritic hip from purulent arthritis, who were treated by muscle release operation, were reported. First case was a 12 year-old-girl, who suffered purulent arthritis on her left hip at 3 years, and began to have ambulatory pain from 12 years. The second case was a 12 and 1/2-year-old girl. She suffered purulent arthritis on her left hip at 12 years and received capsulotomy and drainage. After 6 months she complained of hip pain and gait difficulty. The two cases were treated by muscle release operation following Voss's or O'Malley's procedure. After the operation they obtained good range of motion and excellent X-ray findings on their affected hips.

Factors predicting the outcome of chronic pain management at aN AMBULATORY PAIN CLINIC

Factors predicting the outcome of chronic pain management at aN AMBULATORY PAIN CLINIC