Cases reported "Pain, Intractable"

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1/11. Preliminary evaluation of a fixed dose of zwitterionic piperazine (TVZ-7) in clinical cancer.

    One of the zwitterion buffers that has shown significant therapeutic value in the treatment of pain due to cancer, immunologically mediated diseases, and the pain associated with these conditions is in the class of N-substituted amino-sulfonic acids known as "Good buffers." Zwitterion molecules have neither a negative nor a positive charge; thus, they are neutral. 4-(2 Hydroxyethyl)-1-piperazine ethane sulfonic acid has been used for several decades in artificial biological systems (tissue culture) as a buffer. We have been exploring the therapeutic value of these zwitterionic buffers. Pilot animal studies have demonstrated that zwitterionic piperazine increases bone marrow hypercellularity and induces extramedullary hematopoiesis. We report the initial human use to explore dose toxic and physiologic effects of a fixed dose of the zwitterionic piperazine molecule. There appears to be potential therapeutic value in the treatment of pain due to cancer, and there are preliminary indications that tumor activity and tumor size are reduced. Immunologically mediated diseases may also be affected. Toxicity is low and there appear to be minimal side effects.
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2/11. diphenhydramine as an analgesic adjuvant in refractory cancer pain.

    Clinical and animal data suggest that antihistamines may have efficacy in the management of pain. While many mechanisms of action have been proposed for the analgesic action of antihistamines, the exact mechanism is unknown. Controlled clinical trials in different pain models have demonstrated that antihistamines have direct and adjuvant analgesic activity. We report three patients with advanced cancer pain refractory to adjuvants and oral, intravenous, and epidural opioids, who achieved sustained pain relief after the repeated administration of diphenhydramine. diphenhydramine may be useful in the treatment of neuropathic and nociceptive pain that has failed to respond to treatment with opioids and adjuvant analgesics. We suggest a starting dose of 25 mg of oral or parenteral diphenhydramine every 6 to 8 hours, with titration to effect.
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3/11. analgesia for pelvic and perineal cancer pain by intrathecal steroid injection.

    BACKGROUND: Corticosteroids are used systemically in patients with advanced cancer to alleviate pain. Intrathecal administration of steroids is rarely performed but analgesic effects of intrathecal steroids have been reported in animal studies. We administered betamethasone intrathecally in three cancer patients with uncontrollable pain. CASE REPORT: Intrathecal injection of betamethasone (1-4 mg) with saline (total volume = 2 mL) was performed in three patients with advanced pelvic or perineal cancer, in whom pain could not be controlled in spite of various analgesic therapies. After obtaining the patient's informed consent for the procedure, betamethasone was administered intrathecally through the L4/5 intervertebral space. Intrathecal betamethasone produced rapid analgesia within 10 min and subsequent long-lasting analgesia for 5 days or more. sleep, appetite and activity improved. No adverse effects were observed in any of the patients. CONCLUSIONS: Intrathecal injection of betamethasone may be a useful approach in some patients with intractable cancer pain.
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4/11. hand wound caused by an active sting with a toxin spine of a catfish (Heteropneustes fossilis)--a case report.

    A case of a 33-years-old aquarist admitted to the Clinic with a painful wound caused by a Stinging Catfish (Heteropneustes fossilis) was presented. While cleaning the aquarium the fish actively stung him in the hand. After irrigating and debriding of the wound the patient was given tetanus anatoxin and antibiotic course. The opioid analgesia and local anesthesia had to be provided to relieve the pain. The follow up after 2 weeks showed healed wound of the hand and the patient had no subjective complaints. There is an urgent need for a bill about venomous and poisonous animals which will be allowed to be kept at home. The registration of venomous and poisonous animals in the Regional poison control centers should be compulsory. There is a need for initiating educational activity among people who keep dangerous animals at home as their pets.
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5/11. spinal cord stimulation is an effective treatment for the chronic intractable visceral pelvic pain.

    OBJECTIVE: Recent studies have demonstrated significant involvement of dorsal column pathways in transmission of visceral pelvic pain. spinal cord stimulation (SCS) suppresses visceral response to colon distension in an animal model and therefore may be an effective therapy for chronic pelvic pain of visceral origin. We are reporting on the value of neurostimulation for chronic visceral pelvic pain in six female patients with the diagnosis of long-standing pelvic pain (history of endometriosis, multiple surgical explorations, and dyspareunia). DESIGN AND SETTINGS: Case-series report. All patients received repeated hypogastric blocks (in an average of 5.3 blocks) with a significant pain relief for a period ranging from 1 to 6 weeks. Three received neurolytic hypogastric block with the pain relief of 3, 8, and 12 months, respectively. Following psychological evaluation and clearance by our Multidisciplinary Committee on Implantable Devices, they all underwent SCS trial for 7-14 days. All patients received SCS systems with dual leads (Compact or Quad leads, Medtronic Inc., Minneapolis, MN, USA). RESULTS: The average follow-up was 30.6 months. Median visual analog scale pain score decreased from 8 to 3. All patients had more than 50% of the pain relief. Pain Disability Index changed from an average of 57.7 /- 12 to 19.5 /- 7. Opiate use decreased from an average 22.5 mg to 6.6 mg of morphine sulfate milligram equivalents per day. CONCLUSION: It appears that SCS may have a significant therapeutic potential for treatment of visceral pelvic pain.
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6/11. Control of pain by direct electrical stimulation of peripheral nerves.

    Our results after implanting electrodes around peripheral nerves in 69 patients over a 10 year period are only fair with but 17 individuals maintaining relief until death or until the present time. Thirteen others had weeks or months of temporary relief. A continuing use of transcutaneous and better still of percutaneous electrodes to guide the decision regarding implantation is almost certainly advisable. Intensive efforts in laboratory animal studies with models of chronic pain are needed to improve our understanding of exactly what we should be doing. Empirical sustained work with the individual patient is likely to improve the figures we have presented, even in our present state of ignorance.
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7/11. Myoclonic spasms following intrathecal morphine.

    Myoclonic twitching in the lower limbs of a patient who received intrathecal narcotics is described. There was no loss of consciousness. Reports of this phenomenon in animals are reviewed.
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8/11. Clinical efficacy of methadone in patients refractory to other mu-opioid receptor agonist analgesics for management of terminal cancer pain. Case presentations and discussion of incomplete cross-tolerance among opioid agonist analgesics.

    BACKGROUND. Development of tolerance to opioid analgesics occurs often in patients with cancer-related pain. Cross-tolerance among opioid analgesics provides the physician with a major management problem. Incomplete cross-tolerance among opioid analgesics has been demonstrated to occur in animals and humans. The current study provides clinical evidence of the incomplete cross-tolerance of methadone with a number of mu-opioid agonist analgesics in patients with advanced cancer-related pain. RESULTS. patients presented in the current study had cancer-related pain refractory to other mu--opioid receptor agonist analgesics as evidenced by inadequate analgesia despite escalation of opioid dose. All patients were adequately managed by conversion of their opioid dose to methadone. Additionally, the dose of methadone required to establish and maintain analgesia in these patients was modest compared with previous opioid dose requirements. CONCLUSIONS. methadone is a potent opioid analgesic that demonstrates incomplete cross-tolerance with other mu-opioid receptor agonist analgesics. Conversion of the opioid-tolerant patient with cancer-related pain to methadone may represent an important therapeutic option in the management of patients with this difficult problem.
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9/11. Subarachnoid adrenal medullary transplants for terminal cancer pain. A report of preliminary studies.

    BACKGROUND: The prolonged use of opioids to treat intractable pain with currently available therapeutic modalities is often unsatisfactory, usually because of tolerance or complications. Extensive studies carried out in the authors' laboratories have indicated that the transplantation of adrenal medullary tissue into the spinal subarachnoid space can significantly reduce pain in animal pain models, most likely via release of opioid peptides and catecholamines. The current study was undertaken to assess the feasibility and efficacy of subarachnoid adrenal medullary transplantation in alleviating terminal cancer pain in humans. methods: Two milliliters of human adrenal medullary tissue were prepared in the laboratory and then transplanted via lumbar puncture into the subarachnoid space in five patients suffering from terminal cancer pain. Pain scores (VAS), functional activity, and opioid intake were assessed and recorded before and after the transplantation procedure. In addition, CSF samples were collected before and (when possible) at fixed intervals after transplantation for biochemical and cytologic analysis. RESULTS: Four of the five patients demonstrated progressive decreases in pain scores after the transplant procedure, with concomitant reductions in opioid intake. Three of these four patients remained pain free, two for over 10 months, while the other had a recurrence of her pain after surgery for spinal cord compression secondary to metastases 10 weeks after transplant. The fifth patient had no pain reduction by 1 month after the procedure, and refused further followup. After the transplants, spinal CSF samples revealed increased concentrations of met-enkephalin in three of the five patients, and increased concentrations of catecholamines in the four patients in whom they were determined. CONCLUSIONS: The results obtained in this study indicate that subarachnoid adrenal medullary transplantation may provide a unique and effective approach to the management of intractable chronic pain in humans.
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10/11. hyperalgesia and myoclonus in terminal cancer patients treated with continuous intravenous morphine.

    Eight cancer patients in the terminal stages of the disease treated with high doses of intravenous morphine developed hyperalgesia. All cases were retrospectively sampled from three different hospitals in Copenhagen. Five patients developed universal hyperalgesia and hyperesthesia which in 2 cases were accompanied by myoclonus. In 3 patients a pre-existing neuralgia increased to excruciating intensity and in 2 of these cases myoclonus occurred simultaneously. Although only few clinical descriptions of the relationship between hyperalgesia/myoclonus and high doses of morphine are available, experimental support from animal studies indicates that morphine, or its metabolites, plays a causative role for the observed behavioural syndrome. The possible mechanisms are discussed and treatment proposals given suggesting the use of more efficacious opioids with less excitatory potency in these situations.
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