Pain
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Recent studies have suggested that morphine-3-glucuronide (M3G) may antagonize the analgesic effects of morphine and morphine-6-glucuronide (M6G). To investigate this hypothesis, steady-state concentrations of morphine, M6G and M3G in serum and cerebrospinal fluid (CSF) were measured in 11 patients receiving chronic morphine therapy (9 orally and 2 subcutaneously) for treatment of cancer-related pain. All patients appeared to have morphine-resistant pain and had elected to proceed to intrathecal bupivacaine or percutaneous cordotomy. ⋯ The median molar ratios for CSF/serum distribution of morphine, M6G and M3G were 1.23, 0.12 and 0.14, respectively. Thus, despite their relatively poor ability to penetrate into the CSF, the high serum concentrations of M6G and M3G resulted in substantial concentrations of these metabolites in the CSF. Nevertheless, M3G/M6G ratios in our morphine-resistant patients were similar to published values in patients with well-controlled pain, suggesting that the hypothesis that M3G plays a major role in morphine-resistance is not correct.
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Idiosyncrasies of trigeminal neuralgia provide both clues and constraints on candidate hypotheses concerning the underlying neural mechanism. After reviewing the key clinical aspects of the disease, we propose here a novel hypothesis based on recent findings from experimental nerve-injury preparations. The hypothesis states that trigger stimuli set off bursts of activity in a small cluster of trigeminal ganglion (TRG) neurons that have been rendered hyperexcitable as a result of TRG or trigeminal root damage. ⋯ After a brief period of autonomous firing (seconds to minutes), activity is quenched and a refractory period is initiated by an intrinsic suppressive (hyperpolarizing) process engaged as a result of the rapid firing. The primary abnormality resides in the TRG and trigeminal root, rather than in the skin or the CNS. Because of this, sensation is essentially normal between periods of ectopic paroxysmal TRG discharge.
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Case Reports Randomized Controlled Trial Clinical Trial
Response of chronic neuropathic pain syndromes to ketamine: a preliminary study.
Hyperactivity of N-methyl-D-aspartate (NMDA) receptors may be one of the factors in the genesis of neuropathic pain. Ketamine is an NMDA-blocking agent widely used in human medicine. Ketamine (at 250 mcg/kg i.v. slow push) was administered to 6 patients for control of chronic neuropathic pain syndromes in double-blind placebo-controlled fashion. ⋯ Continuous subcutaneous infusion of ketamine administered to 1 patient with PNS-related neuropathic pain caused no additional improvement in pain control but caused intolerable cognitive and memory side effects. In contrast, side effects during single-dose injections were mild and well tolerated. Ketamine affected the evoked pain and associated after-sensation in chronic neuropathic pain syndromes more than the ongoing constant pain.
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Cryoanalgesia, the technique of freezing peripheral nerves, is used clinically for the treatment of postoperative and chronic pain. Paradoxically, this same technique produces characteristics in a rat model suggestive of neuropathic pain. We have developed a peripheral neuropathy model by freezing the proximal sciatic nerve (sciatic cryoneurolysis, SCN) using a cryoprobe cooled to -60 degrees C in a 30/5/30 sec freeze-thaw-freeze sequence. ⋯ The transient time course of certain behaviors including hypoesthesia and possible return of limb sensation, autotomy, touch-evoked allodynia, foot edema and the presence of spontaneous nociceptive behaviors demonstrate a multiple phase nociceptive process. The temporary nature of these nociceptive behaviors is in sharp contrast to the prolonged bilateral mechanical allodynia evident when these behaviors subside. The surgical anesthetics used during the SCN procedure are shown to variably alter or suppress autotomy following SCN.(ABSTRACT TRUNCATED AT 250 WORDS)