Brain dynamics for perception of tactile allodynia (touch-induced pain) in postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a debilitating chronic pain condition often accompanied by a sensation of pain when the affected region is touched (tactile allodynia). Here we identify brain regions involved in stimulus-induced touch-evoked pain (dynamical mechanical allodynia, DMA), compare brain activity between DMA and spontaneous pain (described earlier for the same patients in [Geha PY, Baliki MN, Chialvo DR, Harden RN, Paice JA, Apkarian AV. Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy. Pain 2007;128:88-100]), delineate regions that specifically code the magnitude of perceived allodynia, and show the transformation of allodynia-related information in the brain as a time-evolving network. Eleven PHN patients were studied for DMA and its modulation with Lidoderm therapy (patches of 5% lidocaine applied to the PHN affected body part). Continuous ratings of pain while the affected body part was brushed during fMRI were contrasted with non-painful touch when brushing was applied to an equivalent opposite body site, and with fluctuations of a bar observed during scanning, at three sessions relative to Lidoderm treatment. Lidoderm treatment did not decrease DMA ratings but did decrease spontaneous pain. Multiple brain areas showed preferential activity for allodynia. However, mainly responses in the bilateral putamen and left medial temporal gyrus were related to the magnitude of allodynia. Both DMA and spontaneous pain perceptions were best represented within the same sub-cortical structures but with minimal overlap, implying that PHN pain modulates behavioral learning and hedonics. These results have important clinical implications regarding adequate therapy.

Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy.

Postherpetic neuralgia (PHN) is a debilitating chronic pain condition, yet there is a lack of knowledge regarding underlying brain activity. Here we identify brain regions involved in spontaneous pain of PHN (n=11) and determine its modulation with Lidoderm therapy (patches of 5% lidocaine applied to the PHN affected body part). Continuous ratings of fluctuations of spontaneous pain during fMRI were contrasted to ratings of fluctuations of a bar observed during scanning, at three sessions: (1) pre-treatment baseline, (2) after 6h of Lidoderm treatment, and (3) after 2 weeks of Lidoderm use. Overall brain activity for spontaneous pain of PHN involved affective and sensory-discriminative areas: thalamus, primary and secondary somatosensory, insula and anterior cingulate cortices, as well as areas involved in emotion, hedonics, reward, and punishment: ventral striatum, amygdala, orbital frontal cortex, and ventral tegmental area. Generally, these activations decreased at sessions 2 and 3, except right anterior insular activity which increased with treatment. The sensory and affective activations only responded to the short-term treatment (6h of Lidoderm); while the ventral striatum and amygdala (reward-related regions) decreased mainly with longer-term treatment (2 weeks of Lidoderm). Pain properties: average magnitude of spontaneous pain, and responses on Neuropathic Pain Scale (NPS), decreased with treatment. The ventral striatal and amygdala activity best reflected changes in NPS, which was modulated only with longer-term treatment. The results show a specific brain activity pattern for PHN spontaneous pain, and implicate areas involved in emotions and reward as best reflecting changes in pain with treatment.

The impact of nalmefene on side effects due to intrathecal morphine at cesarean section.

Nalmefene is a long-acting opioid antagonist that provides long-term relief from side effects of intrathecal morphine sulfate. A randomized, double-blind, placebo-controlled study was conducted to determine whether prophylactic nalmefene could decrease side effects of intrathecal morphine given during cesarean section, without affecting analgesia. Sixty parturients were given 0.25 mg of intrathecal morphine, 12.5 micrograms of fentanyl, and 11.25 to 15 mg of bupivacaine. A dose of 0.25 microgram/kg of nalmefene or placebo was given by intravenous piggyback immediately after delivery of the neonate. Nausea, vomiting, pruritus, and level of sedation were assessed for a 24-hour period using a 4-point ordinal scoring system. Pain was assessed by using a 0- to 10-point verbal analogue scale. A 5-point analgesic satisfaction survey also was completed. Subjects who received nalmefene required supplemental analgesia at a median of 6.00 hours after intrathecal morphine, compared with 14.12 hours in the placebo group (P = .037). No differences were found between the groups in the incidence of pruritus, nausea and vomiting, level of sedation, or analgesic satisfaction. We concluded that nalmefene at a dose of 0.25 microgram/kg does not decrease the incidence of side effects but increases the need for supplemental analgesics.

Topical capsaicin in the management of HIV-associated peripheral neuropathy.

Distal symmetrical peripheral neuropathy (DSPN) is a particularly distressing pain syndrome associated with human immunodeficiency virus (HIV) disease. Capsaicin has been found to be effective in relieving pain associated with other neuropathic pain syndromes, and is mentioned as a possible topical adjuvant analgesic for the relief of DSPN. This multicenter, controlled, randomized, double-masked clinical trial studied patients with HIV-associated DSPN and compared measures of pain intensity, pain relief, sensory perception, quality of life, mood, and function for patients who received topical capsaicin to the corresponding measures for patients who received the vehicle only. Twenty-six subjects were enrolled in the study. At the end of 1 week, subjects receiving capsaicin tended to report higher current pain scores than did subjects receiving the vehicle (Mann-Whitney test; P = 0.042). The dropout rate was higher for the capsaicin group (67%) than for the vehicle group (18%) (chi 2 test of association; P = 0.014). There were no other statistically significant differences between the capsaicin and vehicle groups with respect to current pain, worst pain, pain relief, sensory perception, quality of life, mood, or function at study entry or at any time during the 4-week trial. These results suggest capsaicin is ineffective in relieving pain associated with HIV-associated DSPN.

Efficacy of a vibratory stimulus for the relief of HIV-associated neuropathic pain.

Pain related to HIV disease is frequently debilitating. Of the many pain syndromes that occur in persons with HIV, distal symmetrical polyneuropathy (DSPN) is particularly devastating. Because DSPN often responds, at best, only partially to available pharmacologic interventions, non-pharmacologic interventions need to be investigated. Vibration has been suggested to be effective for reducing pain in other populations with chronic pain. This randomized, sham-controlled, double-masked study tested the short-term efficacy of a 45-min vibration treatment for DSPN foot pain in persons infected with HIV. Vibration therapy was delivered using a portable platform foot vibrator that provided stimulation at a frequency of 60 Hz. For all patients, the control box for the vibrator emitted an audible hum and part of the control box lit up during treatment, but only patients randomized to active treatment received vibration. Pain intensity (0-10) was measured immediately prior to and after treatment. Subjects were also questioned regarding pain relief (0-100%) immediately after the treatment. The mean percentage pain relief was 61.0+/-33.1% (median 70.0; range 0-100) for all patients, 67.3+/-34.0% (median 80.0; range 0-100) for vibration patients, and 55.0+/-32.0% (median 60.0; range 0-100) for sham patients. No statistically significant differences were found between the vibration and sham groups with respect to percentage pain relief (Mann-Whitney test; P=0.19) or the pre- and post-treatment current-pain difference (Mann-Whitney test; P=0.92). These results underscore the necessity for control groups in studies of non-pharmacologic therapies for pain.

Adverse effects associated with the intrathecal administration of ziconotide.

The omega-conopeptide, ziconotide, is an N-type calcium-channel blocker that has been shown to produce antinociception in animals using formalin and hot-plate tests. Initial reports of intrathecal administration of ziconotide in cancer and AIDS patients whose pain was unrelieved with opioids demonstrated analgesic efficacy. Although adverse effects were reported, these appeared to be easily managed through dose reduction or symptomatic treatment. This clinical report describes the experiences of three patients with serious adverse effects associated with intrathecal ziconotide.

Catheter port cleansing techniques and the entry of povidone-iodine into the epidural space.

PURPOSE/OBJECTIVES: To determine whether three epidural catheter port cleansing techniques used to apply a povidone-iodine solution differed with respect to the introduction of this solution through the epidural catheter. DESIGN: Experimental. SETTING: Laboratory. SAMPLE: Five DuPen (Davol, Cranston, RI) epidural catheters. METHODS: Five DuPen epidural catheters each were cleansed twice with (a) a commercially available 10% povidone-iodine swabstick, (b) a commercially available pledget impregnated with 10% povidone-iodine, and (c) a gauze pad saturated with 10% povidone-iodine. The order of cleansing was randomized. Each solution was used to clean the port for 30 seconds, and the port was allowed to dry for 30 seconds, similar to the technique used in the clinical setting. After cleaning the catheter port, water was injected through the catheter, and the solution from the tip of the catheter was analyzed using absorbance spectrophotometry. MAIN RESEARCH VARIABLES: Cleansing techniques, presence of povidone-iodine in catheter. FINDINGS: A statistically significant difference existed between the three cleansing techniques, with the pledget yielding the lowest values of povidone-iodine contamination of the epidural catheter (Freidman test, p = 0.02). CONCLUSIONS: Use of pledgets allowed the least amount of povidone-iodine to enter the epidural catheter as compared with the swabsticks or gauze pads. IMPLICATIONS FOR NURSING PRACTICE: Commercially available pledgets used to cleanse catheter injection ports may limit the introduction of 10% povidone-iodine into the epidural or intrathecal space.

Treatment of low back pain with intraspinal opioids delivered via implanted pumps.

Low back pain, more recently defined as "failed back surgery syndrome" is a common, yet devastating, pain complaint. Although physical therapy and systemic analgesics provide relief in most patients, intraspinal opioids delivered via implanted pumps may be indicated in those individuals who cannot tolerate oral medications. Orthopaedic nurses are essential in the identification and care of patients who might benefit from this therapy.

Barriers to cancer pain relief: fear of tolerance and addiction.

The purposes of this study were to (a) test the feasibility of the Cancer Total Quality Pain Management (TQPM) Patient Assessment Tool in a population of oncology inpatient and outpatients; and (b) identify factors associated with poor pain relief. The Cancer TQPM Tool was adapted from the American Pain Society's Quality Assurance Standards on Acute Pain and Cancer Pain and was tested in a convenience sample of 200 patients. The majority of patients reported that the TQPM Tool was easy to understand and to use, providing evidence for the feasibility of the tool. Factors associated with higher pain intensity included the inpatient setting, the presence of metastatic disease, hesitancy in bothering the nurse, and concerns regarding tolerance and addiction. Although there was a strong relationship between concern about addiction and concern about tolerance, fear of tolerance appeared to have a greater effect on pain intensity scores than did fear of addiction. The findings from this study suggest that the Cancer TQPM Patient Assessment Tool can be used effectively in both inpatients and outpatients to determine outcomes and the quality of cancer pain management, as well identify factors associated with poor pain control. Clinical implications include more effective education of patients and caregivers, including equivalent emphasis on tolerance and addiction.

Quality of life: effect of reduced spasticity from intrathecal baclofen.

Severe, uncontrolled spasticity resulting from spinal cord injury (SCI) and multiple sclerosis (MS) can have a profound effect on the patient's ability to function and thus, their quality of life. Spasticity can be dramatically reduced by the continuous infusion of baclofen into the lumbar subarachnoid space using a drug delivery system. The aim of this study was to explore the effect of reduced spasticity on quality of life using intrathecal baclofen therapy. Twenty-five patients with intractable spasticity treated with intrathecal baclofen participated in this prospective study. Spasticity was measured using the Ashworth and spasm scales. Quality of life was measured using the Ferrans and Powers Quality of Life Index (QLI) and the Sickness Impact Profile (SIP). The mean spasm score decreased significantly from 2.6 at baseline to 0.5 after one year (Friedman test; p = 0.000017). The mean Ashworth score decreased significantly from 3.78 at baseline to 1.48 after one year, (Friedman test; p = 0.00000014). Though total QLI scores were not significantly different when comparing baseline with one year, the SIP revealed significant changes in the total score as well as the physical and psychosocial subscales. It is likely the QLI did not demonstrate improvement in quality of life due to the emphasis of this tool on nonphysical domains. A qualitative analysis of two open-ended questions revealed positive statements about the change in quality of life when spasticity is well-controlled. Measuring changes in quality of life after specific interventions is a difficult task, requiring an accurate operational definition of the concept and valid instruments for measurement.

HIV-associated distal symmetrical polyneuropathy: clinical features and nursing management.

DSPN is a common manifestation of HIV infection and/or its treatment that can have adverse effects on quality of life and functional status. The pathogenesis remains unclear but likely involves the elaboration of neurotoxic inflammatory cytokines and their metabolites. DSPN is often refractory to available pharmacological treatments, although new treatments involving NGF hold promise for effecting sustained symptom relief and reversing axonal degeneration. Further research is needed to determine the efficacy of nonpharmacological treatments, such as cognitive-behavioral therapies, to alleviate DSPN-associated pain.

Clinical realities and economic considerations: efficacy of intrathecal pain therapy.

Studies of analgesia in cancer patients have revealed that intrathecal administration of opioids can deliver potent analgesia with fewer systemic side effects than equivalent doses of systemic opioids. In addition, several trials have examined the safety and efficacy of this modality in patients with pain of nonmalignant origin. In one survey of 35 physicians involving 429 patients treated with intrathecal therapy, physician reports of global pain relief scores were excellent in 52.4% of patients, good in 42.9%, and poor in 4.8%. In another study of 120 patients, the mean pain intensity score had fallen from 93.6 to 30.5 six months after initiation of therapy. In both studies, patients reported significant improvement in activities of daily living, quality of life measures, and satisfaction with the therapy. Constipation, urinary retention, nausea, vomiting, and pruritus are typical early adverse effects of intrathecal morphine and are readily managed symptomatically. Other potential adverse effects include amenorrhea, loss of libido, edema, respiratory depression, and technical issues with the intrathecal system.

Clinical realities and economic considerations: economics of intrathecal therapy.

The estimated annual cost of medical management of chronic back pain is $25 billion. Such management is often ineffective and overly costly. Most physicians who have employed intrathecal pain therapy attest to its efficacy in the management of intractable chronic pain. However, few economic analyses are available to evaluate the cost effectiveness of different modalities and to aid in clinical decision making and third-party reimbursement policies. Current analyses tend to focus on short-term cost-benefit measurements and to ignore variables such as quality of life and patient functioning. This bias has impaired the ability of payers to make appropriate decisions regarding the safety, cost effectiveness, and efficacy of intrathecal pain therapy in noncancer patients. Clinical data demonstrate that for cancer patients whose expectancies exceed 3 months, the overall costs of intrathecal pain therapy may be less than those of tunneled epidural catheters or external infusion devices. In nonmalignant pain, intrathecal therapy appears to be cost effective compared to conventional medical management at 22 months. Further debate and fine tuning of these economic models from all perspectives are required.

Validity of a verbally administered numeric rating scale to measure cancer pain intensity.

The ability to quantify pain intensity is essential when caring for individuals in pain in order to monitor patient progress and analgesic effectiveness. Three scales are commonly employed: the simple descriptor scale (SDS), the visual analog scale (VAS), and the numeric (pain intensity) rating scale (NRS). Patients with English as a second language may not be able to complete the SDS without translation, and visually, cognitively, or physically impaired patients may have difficulty using the VAS. The NRS has been found to be a simple and valid alternative in some disease states; however, the validity of this scale administered verbally, without visual cues, to oncology patients has not yet been established. The present study examined validity of a verbally administered 0-10 NRS using convergence methods. The correlation between the VAS and the NRS was strong and statistically significant (r = 0.847, p < 0.001), supporting the validity of the verbally administered NRS. Although all subjects were able to complete the NRS and SDS without apparent difficulty, 11 subjects (20%) were unable to complete the VAS. The mean opioid intake was significantly higher for the group that was unable to complete the VAS (mean 170.8 mg, median 120.0 mg, SD = 135.8) compared to the group that had no difficulty with the scale (mean 65.6 mg, 33.0 mg, SD = 99.7) (Mann-Whitney test, p = 0.0065). The verbally administered 0-10 NRS provides a useful alternative to the VAS, particularly as more contact with patients is established via telephone and patients within the hospital are more acutely ill.

Animal models in pain research.

OBJECTIVES: To describe the various models of acute and chronic pain used in animal research and to assist the clinical nurse to understand specific terminology in interpreting the research findings. DATA SOURCES: Review articles, book chapters, research studies, and research guidelines and handbooks pertaining to use of animals in laboratory research. CONCLUSIONS: The value of pain research in animals is the testing of new drugs and treatments that may one day be used to relieve pain. Additional benefits include a greater understanding of the physiology of pain and the reflexive and complex pain behaviors that can be used to increase awareness of the human pain experience. IMPLICATIONS FOR NURSING PRACTICE: Understanding the models used in animal research allows greater communication between nurses and scientists, fostering the development of clinically based research questions. Patients with benefit from animal research when nurses and other health care providers appropriately interpret and apply this valuable information in the clinical setting.

Effects of intrathecal nonnarcotic analgesics on chronic tactile allodynia in rats: alpha 2-agonists versus somatostatin analog.

The effects of the intrathecal alpha 2-agonists tizanidine and clonidine and the somatostatin analog octreotide on an experimental rat model of tactile allodynia were investigated to determine the therapeutic potential for treating chronic neuropathic pain. Allodynia was induced by ligating the rat sciatic nerve. The mechanical threshold for paw withdrawal was assessed by applying von Frey hairs to quantify analgesic actions. Mean 50% paw withdrawal thresholds were converted to the percentage of maximum possible effect (%MPE) where %MPE = (postdrug threshold-predrug threshold) divided by (15 g-predrug threshold) x 100. Dose-response curves were plotted for suppression of paw withdrawal 30 minutes after intrathecal injection of various doses of tizanidine, clonidine, and octreotide. Thresholds on the non-lesioned side were greater than 15 g. The lesioned side had baseline thresholds of less than 4.5 g. Dose-response curves were established for the antiallodynia effects of each drug. Tizanidine and clonidine at a 25-micrograms dose increased the threshold to greater than 97% of the MPE, but caused transient hindpaw weakness or sedation. No side effect was observed at a 10-micrograms dose, at which the threshold was 88-96% of MPE. Intrathecal octreotide modestly increased the threshold to only 49-67% of MPE, showing a lesser analgesic effect, although no side effect was observed at a 4-micrograms dose. The antiallodynic effects of intrathecal tizanidine and clonidine were more potent than that of octreotide.

Intraspinal morphine for chronic pain: a retrospective, multicenter study.

Intraspinal opioids are frequently used in the treatment of cancer and noncancer pain, but few studies have evaluated the efficacy of this technique. This multicenter, retrospective study surveyed physicians in the United States regarding their standard practices when using intraspinal opioids delivered via an implanted drug administration device. Thirty-five physicians (50.0%) responded, providing 429 usable patient forms (52.4%), which sought information about screening, outcomes, dosing, and adverse effects. Patients with malignant (32.7%) and noncancer (67.3%) pain had been treated for an average of 14.6 +/- 0.57 months (range, 8-94 months) at the time of form completion. For all patients, the mean percent relief was 61.0% +/- 1.35%. Patients with somatic pain tended to have greater relief, as measured by a global rating of pain relief, than did patients with other types of pain (Mann-Whitney test, P = 0.0003). After titration during the first 3 months, intrathecal morphine doses increased only twofold from 6.84 +/- 0.65 mg/day at 3 months to 13.19 +/- 1.76 mg/day at 24 months. Compared to those with noncancer pain, malignant pain patients had a higher average initial dose. The average dose used by cancer patients escalated quickly and then stabilized, whereas the average doses used by noncancer pain patients exhibited a more gradual, linear increase in dose. Long-term adverse drug effects were uncommon, but system malfunction, usually catheter related, occurred in 21.6% of patients. Prospective, randomized, controlled clinical studies of long-term efficacy and adverse effects are warranted.

Intrathecal octreotide for relief of intractable nonmalignant pain: 5-year experience with two cases.

Somatostatin is distributed in the substantia gelatinosa in the dorsal horn of the spinal cord, and its application has been found to produce an inhibitory effect on nociceptive neurons. Although intraspinal administration of somatostatin-14 produces pain relief in patients with cancer and in postoperative patients, its short half-life limits its clinical usefulness. Octreotide, a synthetic analog of somatostatin, is more stable and not been associated with neurodegenerative changes when administered intrathecally in dogs. Intrathecal octreotide provides analgesia without adverse drug effects when administered chronically for cancer pain; however, treatment periods have been limited. This article describes the 5-year clinical course of two patients receiving intrathecal octreotide for severe, intractable nonmalignant pain. Included in this description are the results of blinded, randomized "N of 1" trials conducted in each of these patients.