Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial.

The mechanisms underlying central neuropathic pain are poorly understood. Pain inhibitory mechanisms including sertononergic and norepinephrine systems may be dysfunctional. In this randomized, double-blinded, placebo-controlled trial we evaluated the effects of duloxetine on pain relief (spontaneous pain and evoked pain), tolerability, health status, and quality of life in patients with central pain related to cerebrovascular lesions or spinal cord lesions. At baseline and eight weeks following start of treatment subjects were evaluated with standard measures of efficacy: pain intensity (primary efficacy variable), quantitative sensory testing, health status and quality of life (secondary efficacy variables). Forty-eight patients received escalating doses of either duloxetine (60 and 120mg/day) or matching placebo capsules. In both groups, patients started with 1 capsule per day. If pain relief was insufficient, patients were titrated to a higher dose. A trend towards a decrease in mean pain score after eight weeks was observed for duloxetine treatment (p=0.056). Duloxetine alleviated dynamic (p=0.035) and cold allodynia (p<0.001) significantly better than placebo. Tactile pain and pressure pain thresholds did not improve significantly. The duloxetine group showed a significant improvement for the bodily pain domain of the SF36 (p=0.035). No significant differences were observed in the other domains of the SF36, the Pain Disability Index, and the EQ-5D. While this trial showed no significant effect on pain intensity, duloxetine revealed a biologic effect. It would be worthwhile to suspend our judgement and to perform more studies to evaluate the role of duloxetine in modulation of the symptoms of central neuropathic pain.

Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen.

The effective treatment of patients suffering from central neuropathic pain remains a clinical challenge, despite a standard pharmacological approach in combination with anticonvulsants and antidepressants. A randomized, double-blinded, placebo-controlled trial evaluated the effects of pregabalin on pain relief, tolerability, health status, and quality of life in patients with central neuropathic pain caused by brain or spinal cord injuries. At baseline and 4 weeks after the start of treatment subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analog scale, health status (Pain Disability Index and EQ-5D) and quality of life (SF-36). Forty patients received escalating doses of either pregabalin (150, 300, and 600mg/day) or matching placebo capsules. In both groups, patients started with 1 capsule per day (either 150mg of pregabalin or placebo). If pain relief was insufficient, patients were titrated to a higher dose. There was a statistically significant decrease in mean pain score at endpoint for pregabalin treatment, compared with placebo (P=0.016). Follow-up observation showed no significant difference in Pain Disability Index scores between the two groups. The pregabalin group, however, showed a statistically significant improvement for the EQ-5D. Pregabalin treatment led to a significant improvement in the bodily pain domain of the SF36. In the other domains, more favorable scores were reported without reaching statistical significance. Pregabalin, in a flexible-dose regime, produced clinically significant reductions in pain, as well as improvements in health status in patients suffering from severe central neuropathic pain.

[Coeliac plexus block in patients with pancreatic tumour pain]. / Blokkade van de plexus coeliacus bij patiënten met pijn door een pancreastumor.

Pancreatic cancer tends to be diagnosed at a relatively late stage of the disease when curative resection is precluded. In view of the poor prognosis and the severe pain, palliative care should be aimed at providing adequate pain relief and optimal quality of life. Pancreatic cancer pain is primarily treated by the combination of NSAIDs, adjuvant analgesic drugs, and oral or transdermal opioids. The neurolytic coeliac plexus block is recommended as adjuvant therapy for the palliative treatment of pancreatic cancer pain. In addition quality of life, especially functional and physical aspects, is significantly improved in patients following a coeliac plexus block. The most common approach to the coeliac plexus is the percutaneous posterior technique. Serious complications that may follow application of this technique include sensory disorders, muscle weakness and paraparesis. More recently, new techniques such as thoracoscopic splanchnicectomy and endoscopic ultrasound-guided coeliac plexus block have emerged as efficient alternatives in terms of pain relief and quality-of-life improvement. The neurolytic coeliac plexus block has become a well-developed method of pain relief in patients with pain resulting from malignancies of the pancreas. To define the role of these new techniques in the palliative treatment of pancreatic cancer pain, comparative studies regarding efficacy, side effects, and complications have to be performed.

Iontophoretic administration of S(+)-ketamine in patients with intractable central pain: a placebo-controlled trial.

The efficacy of 50 and 75 mg S(+)-ketamine administered daily by an iontophoresis-assisted transdermal drug delivery system was tested against placebo in a randomized, double-blind design in 33 patients with central neuropathic pain. At baseline and 1 week after the start of treatment subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analog scale (VAS), health status (Pain Disability Index and EQ-5D) and quality of life (SF-36). Safety assessment included incidence and intensity of adverse events. No significant differences in pain scores (VAS) were observed between the ketamine groups and placebo during the course of the trial. Corrected for baseline levels, daily 50 mg S(+)-ketamine did not improve patient's health status or quality of life compared with placebo treatment. However, daily 75 mg S(+)-ketamine showed significant improvements on the Pain Disability Index, on the EQ-5D, and on the SF-36 except for the role-physical functioning and general health perception. Iontophoretic administration of S(+)-ketamine was well tolerated with a low incidence of adverse events (mild and transient in nature, resolving spontaneously). Iontophoretic administration of S(+)-ketamine was not more effective than placebo treatment in reducing pain scores in patients with severe central neuropathic pain. However, iontophoretic administration of 75 mg S(+)-ketamine improved the health status and the quality of life in these patients.

Neuropathological findings after continuous intrathecal administration of S(+)-ketamine for the management of neuropathic cancer pain.

Questions have been raised about the potential neurotoxicity of the neuraxial use of ketamine although ketamine and its active enantiomer S(+)-ketamine have been used intrathecally and epidurally (caudally) for the management of perioperative pain and in a variety of chronic pain syndromes. Clinical experience following neuraxial administration of S(+)-ketamine has been documented without reference to local central nervous system toxicity following this approach. In addition, there are no preclinical safety data regarding stability, compatibility, and neurotoxicity on intrathecal use of single S(+)-ketamine or combinations of S(+)-ketamine, morphine, bupivacaine, and clonidine. In the present case, the continuous intrathecal administration of S(+)-ketamine, in combination with morphine, bupivacaine, and clonidine resulted in adequate pain relief in a patient suffering from intractable neuropathic cancer pain. However, postmortem observation of the spinal cord and nerve roots revealed severe histological abnormalities including central chromatolysis, nerve cell shrinkage, neuronophagia, microglial upregulation, and gliosis. Based on our results, neuraxial administration of S (+)-ketamine cannot be recommended for clinical practise before a systematic study of toxicology of neuraxial S(+)-ketamine in animals or humans has been performed.

Plasma concentrations of meperidine and normeperidine following continuous intrathecal meperidine in patients with neuropathic cancer pain.

BACKGROUND: Intrathecal administration of meperidine, an opioid with local anesthetic activity, can induce analgesia in patients with intractable cancer pain. However, continuous intrathecal administration may result in the accumulation of normeperidine, responsible for central nervous system toxicity. METHODS: Ten patients with neuropathic cancer pain, not responding to conventional opioid therapy, were treated with continuous intrathecal administration of meperidine. In all patients, plasma concentrations of meperidine and normeperidine were measured the first days after the start of treatment. Visual analog scale scores were recorded to evaluate pain relief. Quality of life was assessed before and 3 weeks following the start of intrathecal treatment. RESULTS: In three patients the plasma concentrations of meperidine and normeperidine increased rapidly. In one patient the plasma normeperidine concentration was higher than the meperidine concentration. One patient demonstrated transient symptoms suggestive for central nervous system excitation. Three weeks following the start of treatment, seven patients were available for evaluation of their quality of life. Pain relief and overall quality of life improved during the intrathecal treatment. CONCLUSION: We conclude that continuous intrathecal administration of meperidine alone, or in combination with clonidine, can provide significant pain relief in patients with poor pain control despite pharmacological treatment. However, accumulation of meperidine and normeperidine resulting in central nervous system toxicity may occur during this treatment.

Treatment of neuropathic cancer pain with continuous intrathecal administration of S +-ketamine.

The effective treatment of patients suffering from neuropathic cancer pain remains a clinical challenge. When patients experience either insufficient analgesia or problematic side-effects after opioid administration, intrathecal administration of morphine and other medications such as bupivacaine and clonidine may offer significant advantages. Additionally, ketamine, a non-competitive N-methyl-D-Aspartate-receptor antagonist is able to alter pain perception at the spinal level. Because of the potential neurotoxicity after neuraxial use of racemic ketamine, intrathecal administration of the preservative-free active compound, S (+)-ketamine may be a valuable alternative. In this paper, we present a patient with severe neuropathic cancer pain successfully treated by continuous intrathecal infusion of morphine, bupivacaine, clonidine and S (+)-ketamine. Moreover, quality of life measurements before and 3 weeks after the start of spinal treatment revealed an improvement in pain relief and a higher overall quality of life. No clinical signs of neurologic deficit were observed during spinal treatment with S (+)-ketamine. However, the continuous intrathecal administration of S (+)-ketamine should be considered as the last resort because there are no preclinical safety data with relevant concentrations on intrathecal use of S (+)-ketamine.

Neurohistopathologic findings after a neurolytic celiac plexus block with alcohol in patients with pancreatic cancer pain.

Pancreatic cancer has a very poor prognosis resulting in the death of 98% of patients. Pain may be severe and difficult to treat. Management of pain includes chemotherapy, radiotherapy, pharmacologic treatment, and neurolytic celiac plexus block. Recent reviews of the efficacy of neurolytic celiac plexus block however, have reached conflicting conclusions. In this paper, we present two patients with severe pancreatic cancer pain resistant to pharmacologic treatment. Analgesic effect following repeated neurolytic celiac plexus blocks with alcohol was limited in time. Post-mortem neurohistopathologic examination of the celiac plexus revealed an abnormal celiac architecture with a combination of abnormal neurons with vacuolization and normal looking neuronal structures (ganglionic structures and nerve fibers) embedded in fibrotic hyalinized tissue. Our results show that a neurolytic celiac plexus block with alcohol is capable of partially destroying the celiac plexus. These findings may explain the significant but short-lasting analgesic effect following neurolytic celiac plexus block with alcohol.

Increasing the efficacy of a celiac plexus block in patients with severe pancreatic cancer pain.

The purpose of this study was to evaluate the technical possibilities of placing a catheter near the celiac plexus for performance of a celiac plexus block, and to study the efficacy of repeated neurolytic celiac plexus blocks with alcohol in patients with advanced pancreatic cancer pain resistant to opioid treatment. In 12 patients, a neurolytic celiac plexus block with alcohol, administered via an indwelling celiac catheter, was performed. To evaluate the efficacy, visual analog scale scores were recorded every day. Quality of life scores were registered before and 4 weeks following the procedure. Alterations in opioid consumption, and the time between the diagnosis of pancreatic cancer and the performance of the block, were registered. All patients were followed until they died. Two patients remained without pain after the first neurolytic celiac plexus block. In all other patients a second block was administered which provided only temporary relief. Additional intermittent administration of bupivacaine through the catheter was necessary to provide adequate pain relief in these patients. Quality of life increased significantly during the treatment. Opioid consumption decreased significantly in all patients. Our study indicates that a neurolytic celiac plexus blockade with alcohol results in a significant but short-lasting analgesic effect. The use of a celiac catheter improves the long-term management of pancreatic cancer pain.

Continuous brachial plexus block at the cervical level using a posterior approach in the management of neuropathic cancer pain.

BACKGROUND AND OBJECTIVES: Neuropathic cancer pain due to tumor growth near the brachial plexus is often treated with a combination of nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, anticonvulsants, and oral or transdermal opioids. We propose placement of a catheter along the brachial plexus using a posterior approach for patients not responding to the above-mentioned treatment. CASE REPORT: We describe 2 patients with neuropathic cancer pain in the arm and shoulder despite treatment with dexamethasone, amitriptyline, gabapentin, opioids, and, in 1 patient, oral ketamine. An increase in daily opioid dosage did not relieve the pain but caused unacceptable side effects of nausea, vomiting, and sedation. Continuous administration of local anesthetics via a brachial plexus catheter inserted at the cervical level using a posterior approach resulted in a markedly improved analgesia and decreased opioid requirement. CONCLUSION: Continuous brachial plexus block should be considered in patients with severe neuropathic cancer pain in the arm and shoulder. To achieve sufficient pain relief for prolonged periods of time, a catheter was inserted to block the brachial plexus using a posterior approach. This technique may be a valuable alternative to the interscalene approach because of the improved fixation of the catheter in the muscle sheet of the trapezius, splenius cervicus, and levator scapulae muscles, and the decreased likelihood of catheter dislodgment during neck movements.

Intraarticular sufentanil administration facilitates recovery after day-case knee arthroscopy.

UNLABELLED: We evaluated the efficacy of intraarticular sufentanil in the prevention of postoperative pain after day-case arthroscopic procedures. Sixty patients were randomly assigned to receive either intraarticular sufentanil, 5 or 10 microg, and saline IV, or intraarticular saline and sufentanil 5 microg IV (control). All study medication was administered in a double-blinded fashion. Postoperatively and the day after surgery, pain levels at rest and during movement (i.e., active flexion of the knee), measured by a visual analog scale, were significantly lower in the Sufentanil groups compared with the Control group. Moreover, intraarticular sufentanil significantly reduced the postoperative consumption of analgesics. The time until discharge from the postanesthesia care unit (assessed by the Aldrete score) was significantly shorter in the patients receiving sufentanil intraarticularly. There were no significant differences between the two Sufentanil groups either in the intensity of postoperative pain or in discharge times from the postanesthesia care unit. We conclude that intraarticular sufentanil in arthroscopic knee procedures is a simple, effective, safe and well-tolerated analgesic technique for outpatients undergoing arthroscopic procedures. Increasing the dose sufentanil from 5 to 10 microg intraarticularly offered no additional advantage. Intraarticular sufentanil (5-10 microg) administration improves postoperative management after day-case diagnostic arthroscopic knee procedures. IMPLICATIONS: Intraarticular sufentanil (5-10 microg) administration improves postoperative management after day-case diagnostic arthroscopic knee procedures.

Continuous brachial plexus block as treatment for the Pancoast syndrome.

BACKGROUND: Six patients with severe neuropathic pain caused by a Pancoast tumor were treated with the continuous administration of local anesthetics. These patients had not responded to any other treatment, including nonsteroidal anti-inflammatory drugs, opioids, dexamethasone, tricyclic antidepressants, anticonvulsants, ketamine, and transcutaneous electric nerve stimulation. INTERVENTIONS: An axillary catheter was placed in the brachial plexus using a posterior approach that has not been described previously. A continuous infusion system of local anesthetics was delivered via a catheter. In two patients, the main purpose was to evaluate the technical possibilities and implications of this new approach. In all patients, the visual analogue scale score was evaluated until the patient died. In four additional patients, the quality of life and performance skills were recorded. RESULTS: In all patients, there was a significant reduction in the visual analog scale score, and there was an increase in performance skills and quality of life in four patients. No side effects occurred from this technique or from the continuous administration of local anesthetics. CONCLUSIONS: We conclude that neuropathic pain may be treated by local anesthetics administered through an axillary catheter placed in the brachial plexus. This technique is reversible and is preferable to destructive procedures such as cordotomy.