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 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sharp pain is conducted rapidly by myelinated delta A fibers and diffused pain slowly by nonmyelinated C fibers to pseudobipolar neurons in the posterior ganglion and from there to neurons located in the posterolateral horn of the spinal cord. From here on nociferous impulses are transmitted by excitatory peptides (e.g. substance P) or amino acids (e.g. glutamate, aspartate) through interconnecting neurons of the pain pathways, primarily on the contralateral side, to the brain stem and from there to the sensory cortex, where they are appreciated and acted upon. There are specific inhibitory receptors located on axon terminals, near to the release sites of the excitatory amino acids and peptides. Stimulation of these receptors by their appropriate ligands such as endogenous (e.g. enkephalis, endorphins) or exogenous opioids, clonidine, serotonin, somatostatin inhibits the release of excitatory neurotransmitters and relieves pain. There are at least 3 different opioid receptors, called mu-, kappa- and delta-receptors in the spinal cord. These can be differentiated from one another by their specific affinity toward different endogenous or exogenous opioids and the pure narcotic antagonist, naloxone. It appears that the nociferous impulses transmitted by parallel pathways equipped with different inhibitory receptors have to be integrated to produce pain sensation and partial inhibition of transmission in different pathways or complete inhibition in one of the pathways may relieve pain. In recent years the concept of "selective spinal analgesia" has been applied clinically for the relief of postoperative, obstetrical and chronic pain. At first it was expected that the intrathecal or peridural administration of morphine will produce analgesia without the side effects of systemically administered morphine. It soon became evident, however, that intrathecally and peridurally administered morphine after several hours of delay reaches the fourth ventricle and by stimulating mu-receptors may cause respiratory depression and other undesired effects (e.g. nausea, vomiting, pruritus). Several different approaches are being investigated for the production of selective spinal analgesia without side effects. They include: a. the use of more lipophilic, long-lasting opioids (e.g. lofentanil) which would be almost completely absorbed by the spinal cord and therefore would not reach the medullary centers; b. the development of opioids with specific affinity to kappa- and for delta- and little or no affinity to mu-receptors, primarily responsible for side effects; and c. combining lower doses of opioid agonists with alpha 2-adrenergic agonists (e.g. clonidine) or with somatostatin. It is conceivable that in the not-too-distant future, it will be possible to achieve through these measures, selective spinal analgesia without side effects.
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PMID:Pain control with intrathecally and peridurally administered opioids and other drugs. 168 73

Intraspinal narcotic (usually intrathecal morphine) infusions with implanted pumps are increasingly used in patients with intractable chronic pain not caused by cancer. In some patients, pain control is difficult with infusions of morphine. Seven patients with diagnoses of arachnoiditis, epidural scarring, and/or vertebral body compression fracture were treated with alternative solutions in an epidural route. For maximal flexibility, Medtronic implanted programmable infusion pumps with catheters to T6-T10 were used, and pain was monitored by verbal pain scales. In three patients, epidural infusions of morphine in 0.5% bupivacaine (MS-MARC) resulted in little or no pain relief without significant side effects (e.g., headache, nausea, or vomiting). In these same patients, epidural infusions of sufentanil citrate resulted in pain scale reductions of 92%, 82%, and 40%, respectively, with no side effects. Four other patients found more effective pain relief when switched from initial sufentanil citrate infusions to MS-MARC. Pain scale reductions (with no side effects) were 92%, 76%, 59%, and 47% in these patients. Pain relief and minimal side effects with sufentanil citrate is theorized to result from its higher lipophilicity promoting local transdural diffusion to spinal cord and limiting upward diffusion to the brain stem. Sufentanil citrate is also advantageous for programmable pumps because it is 100 times more potent than morphine and therefore allows longer pump refill times and higher infusion doses. Although this study was done on a limited number of patients, sufentanil citrate and MS-MARC in epidural infusions using programmable infusion pumps for non-cancer patients provide significant alternative drug combinations and routes.
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PMID:Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural infusions for intractable non-cancer pain. 183 Dec 48

The use of spinally administered opioids to manage pain is discussed. Central action on opioid receptors of the substantia gelatinosa allows opioids to be administered spinally for pain originating anywhere inferior to the cranial nerves. Spinal opioids are most commonly administered for intractable midline sacral and perineal pain. The best candidates for spinal opioids are patients in whom appropriate "conventional" therapy no longer provides adequate relief, patients who experience severe adverse effects from conventional therapy, and patients for whom alternative anesthetic procedures are inappropriate or have failed. A reasonably safe initial dose is morphine sulfate 1 mg intrathecally. The availability of preservative-free, concentrated morphine sulfate enables larger doses to be safely and comfortably administered. Increased dosage requirements may result from tolerance, progression of disease, increased systemic absorption, or slippage of the catheter tip. As with systemically administered opioids, care must be exercised when discontinuing spinal opioid therapy. Adjuvant drugs used with spinal opioids include systemically administered analgesics, antidepressants, corticosteroids, and spinal local anesthetics. The administration of spinal opioids with systemic opioids or other CNS depressants may result in excessive sedation, respiratory depression, nausea, vomiting, constipation, pruritus, and other adverse effects. Spinally administered opioids can be used to manage severe chronic pain effectively, safely, and comfortably.
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PMID:Pain management with spinally administered opioids. 220 8

This randomized, double-blind, multi-centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip. A total of 158 outclinic patients entered the study. Eighty-three patients (mean age 66 years) were treated with codeine 60 mg plus paracetamol 1 g 3 times daily, and 75 patients (mean age 67 years) with paracetamol 1 g 3 times daily. Ibuprofen 400 mg was prescribed as rescue medication. Due to an unexpected high rate of adverse drug reactions, the study was closed before the planned 400 patients had entered. Over weeks 1-4, 87%, 64%, 61% and 52% of patients in the codeine plus paracetamol group, and 38%, 31%, 22% and 29% of patients in the paracetamol group had one or more adverse drug reactions. Significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks. Nausea, dizziness, vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group. During the first week of treatment, 30 patients (36%) in the codeine plus paracetamol group and 9 (12%) in the paracetamol group dropped out. As evaluated from patients completing the first week of treatment, the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group. Moreover, during the first week the paracetamol group received rescue medicine significantly more frequently. In conclusion, when evaluated after 7 days of treatment, the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint. However, several adverse drug reactions, mainly of the gastrointestinal tract, and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine cannot be recommended for longer-term treatment of chronic pain in elderly patients.
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PMID:Codeine plus paracetamol versus paracetamol in longer-term treatment of chronic pain due to osteoarthritis of the hip. A randomised, double-blind, multi-centre study. 229 42

In a randomised double-blind study of 20 patients with chronic pain, epidural morphine 5 mg in 5 ml of saline was compared with epidural clonidine 150 micrograms in 5 ml of saline. Thirteen patients had a clinical and radiological diagnosis of arachnoiditis, 6 had low back pain and 1 had post-operative scar pain. There were 18 females and 2 males with an average age of 52 years, range 22-76 years. There was no difference found between the 2 solutions in the resultant analgesia measured by the visual analogue scale for pain, pain relief or the pain word score during the 3 h period of the study. No difference was found in the patient's mood which was also measured with the visual analogue scale. Two patients had no analgesia from either injection, 2 patients did not obtain any relief from clonidine and another 2 obtained no relief from morphine. Six patients reported that clonidine was better than morphine, 5 reported that morphine and clonidine were the same and 3 reported that morphine was better than clonidine. The duration of analgesia from the clonidine varied from 6 h to 1 month; the duration of analgesia from morphine varied from 6 to 24 h. Clonidine was associated with sedation and a fall in blood pressure of greater than 20 mm Hg in all patients, 1 patient required ephedrine to treat hypotension. Twelve patients had pruritus, 7 nausea and 2 vomiting following the morphine. Statistically there was no difference found between morphine and clonidine for short-term (3 h) analgesia in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A double-blind comparison between epidural morphine and epidural clonidine in patients with chronic non-cancer pain. 317 51

We report the extradural administration of low-dose morphine in 10 ml of 10% dextrose (2-3 mg) to 98 adult patients with various types of acute and chronic pain. Extradural morphine injections were given either via a Tuohy needle (single or repeat injection) or via an extradural catheter. Pain relief was evaluated by subjective scoring and by the subsequent need for systemic analgesics. In 56% of patients, pain relief was considered good or excellent, in 24% it was fair, and in 20%, poor. The best results were after surgery and trauma and in patients with advanced peripheral vascular disease. The analgesia of each dose of extradural morphine lasted for 8 h (mean range 4-36 h). There was no motor, sensory or sympathetic blockade and no respiratory or haemodynamic complications. Dizziness and vomiting occurred in two patients, and urinary retention for about 12 h in three.
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PMID:Observations on extradural morphine analgesia in various pain conditions. 737 Jan 40

Tramadol is effective in treating both acute and chronic pain, exhibiting a potency equivalent to that of pethidine, and it has an acceptable adverse event profile. Whilst the most common adverse events are nausea, vomiting, drowsiness and dizziness, as would be expected from an opioid, there is a noticeable lack of respiratory depression. This latter property, together with its low potential for the development of tolerance and dependence, make tramadol a most interesting agent for clinical use. The studies reported in this article illustrate the beneficial and adverse effects of tramadol to enable the clinician to judge the value of this agent.
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PMID:Chronic pain--challenge and response. 751 24

Complications possibly related to battle injuries are not necessarily discovered immediately postwounding, but may surface many months or years later. Sometimes, the relationship is evident, but often it is difficult to prove the connection. Between 1975 to 1989, we treated 260 veteran wounded from Israel's wars (1948 to 1982). Of these, 122 patients suffered from abdominal complaints, and this study relates only to this group. Eighty percent of them had undergone surgery caused by abdominal trauma at the time of the original injury, and the remaining 20% were injured in areas other than the abdomen. Their complaints manifested several weeks to 35 years postinjury. Diagnosis was delayed for 1 to 8 years in 70% of the patients. Acute or chronic pain, dyspepsia, intolerance to certain foods, early satiety, nausea, vomiting, distension, disturbances in bowel movements, and discharge from unhealed wounds were the most frequently encountered complaints. After evaluation and diagnostic work-up, it was possible to establish diagnosis and afford appropriate treatment in 97 (77%) of the patients. Peptic ulcers were found in 31 patients; 10 required surgery for ulcer-related complications. Acute and repeated attacks of intestinal obstruction occurred in 19 patients; 14 required surgery. The cause of obstruction was adhesions in nine, and strictures, incarcerated hernias, and abscess formation in the rest. Ventral hernias at surgical, ostomy, and drain sites were found and repaired in 49 patients. Abdominal wall sinuses originating from foreign bodies or osteomyelitis were found in 13 patients, and low output enterocutaneous fistulas were found in three patients. Chronic abdominal abscesses were found in 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Late abdominal complications in war wounded. 786 59

Fentanyl is a synthetic opioid with short-acting analgesic activity after intravenous or subcutaneous administration. The low molecular weight, high potency and lipid solubility of fentanyl make it suitable for delivery via the transdermal therapeutic system (TTS). These systems are designed to release the drug into the skin at a constant rate ranging from 25 to 100 micrograms/h, multiple systems can be applied to achieve higher delivery rates. Initially, much of the clinical experience with fentanyl TTS was obtained in patients with acute postoperative pain. However, because of the increased risk of respiratory complications, fentanyl TTS is contraindicated in this setting. Fentanyl TTS is recommended for use in chronic cancer pain. Moreover, in 11 countries worldwide including the US, its use is not restricted to chronic cancer pain; the drug is also available for treatment of general chronic pain, including that of nonmalignant origin. At the start of fentanyl TTS treatment, depot accumulation of the drug within skin tissue results in a significant delay (17 to 48 hours) before maximum plasma concentration is achieved. Approximately half of the cancer patients converted to transdermal fentanyl from other opioid agents required increased dosages after initial application of the patch. However, concomitant use of short-acting morphine maintained pain relief during the titration period, and the use of such supplementary medication decreased with the duration of fentanyl TTS treatment. In patients with chronic cancer pain, changes in visual analogue scale (VAS) pain scores ranged from a 10% increase (worse pain) to > 50% decrease (less pain) during transdermal fentanyl therapy compared with previous opioid treatment. In addition, patient preference for fentanyl TTS was indicated by the number of patient requests (up to 95%) for continued use of the drug at the end of the study. Although fentanyl TTS is contraindicated in patients postoperatively, the efficacy of fentanyl via the transdermal route was investigated in this patient group. Supplementary patient controlled analgesia was significantly reduced in patients who received fentanyl TTS 75 micrograms/h compared with placebo, although this was not apparent until > or = 12 hours after application. Data evaluating pain relief, which was assessed by VAS pain scores, were inconclusive. Preliminary data, although from relatively small numbers of patients, indicate that transdermal fentanyl may be useful in the management of chronic non-malignant pain. Indeed, some patients whose pain was previously uncontrolled became completely pain free. The most frequently occurring adverse events during fentanyl TTS therapy (as with other opioid agents) included vomiting, nausea and constipation, although vomiting and nausea were not clearly associated with the drug. The most serious adverse event was hypoventilation, which occurred more frequently in postoperative (4%) than in cancer patients (2%). In surgical patients, fentanyl-associated respiratory events (reduced respiratory rate and apnoea) generally occurred within 24 hours of patch application; however, there were isolated reports of late onset (> or = 36 hours postsurgery) fentanyl-associated respiratory depression. In cancer patients, the incidence of constipation was reduced by up to two-thirds after switching from oral morphine to transdermal fentanyl. Transient skin irritation associated with the plastic patch or the adhesive, rather than the drug, was reported in a maximum 3% of patients. In summary, transdermal fentanyl is a useful alternative to other opioid agents, which are also recommended on the third step of the WHO analgesic ladder, in the management of chronic malignant pain. Preliminary data indicate that it may be useful in the management of chronic nonmalignant pain. The advantages offered by fentanyl TTS over traditional methods of chronic pain control include its ease of administration, less constipation and the 3-
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PMID:Transdermal fentanyl. A review of its pharmacological properties and therapeutic efficacy in pain control. 901 Jun 52

Pain is the main reason prompting patients to consult their physicians. In acute conditions, pain has a very particular significance as a warning sign, enabling the physician to attempt a diagnosis. Nevertheless, its detrimental effect upon the individual (even in the case of acute pain) and its cost to society are now widely acknowledged. There can be no doubt about the physical component of pain, but the psychological and social aspects should not be ignored, particularly in the case of chronic pain. There is no single therapeutic approach to pain and, more often than not, successful treatment comprises a combination of several. Pharmacological treatments are undeniably the most common approach. In clinical practice, recent advances have been based upon an improved understanding of 'old' substances such as morphine and, at the same time, research continues in the hope of finding the 'ideal' analgesic-effective in most situations but without adverse effects: this appears to be a somewhat utopian arm at present, considering the number of different causes of pain. An improved understanding of the physiological mechanisms of pain has led, within the field of clinical practice, to several methods of differentiating pain. These depend on whether or not pain responds to morphine, or on the type of pain: pain due to an excess of nociception, pain resulting from deafferentation (caused by damage to nerve pathways) in the central or peripheral nervous system and psychogenic (idiopathic) pain. Likewise, there are several different ways of classifying analgesic treatments: according to the intensity of pain, as with use of the WHO ladder (which is based on the notion of steps) for the treatment of cancer pain; according to the presumed physiopathological mechanism and, in particular, the response to morphine, and according to the presumed central or peripheral mechanism of the drugs. In reality, peripherally acting drugs can also have a central mechanism of action, just as drugs known to have a central mechanism of action can also have peripheral activity. As a result, several therapeutic classes have been identified. Firstly NSAIDs, which act by inhibiting the enzymes that synthesise prostaglandins, cyclooxygenases (COX-1, COX-2), but which also act upon lipo-oxygenases: Their efficacy is interesting, although somewhat limited by both their ceiling effect and the frequent adverse gastrointestinal reactions they produce. Specific inhibitors of COX-2 could well reduce the risk of adverse effects. Opioids constitute the first-line treatment for pain, particularly severe pain. There are several classifications for these drugs. Firstly, weak opioids (such as codeine) and strong opioids (such as morphine) are differentiated. Secondly, a distinction is made between pure agonists (such as morphine), partial agonists (such as buprenorphine), agonist-antagonists (such as nalbuphine) and antagonists (such as naloxone). Finally, agents are distinguished on the basis of their chemical structure (synthetic, semi-synthetic or natural derivatives). These molecules act upon different receptors (mu, delta, kappa, sigma) and, although peripheral mechanisms have been described, their activity occurs mainly at spinal and supraspinal levels. They provide a potent analgesic effect but are also responsible for various adverse effects-nausea, vomiting, sedation, constipation and respiratory depression-which seriously limit their use. As long as the indication is appropriate, these drugs should not be withheld because of fear of dependence or abuse. It has been observed that other adjuvant therapeutic approaches, generally used to treat conditions other than pain, provide pain relief in certain situations. These include corticosteroids, which are-widely used in rheumatology and oncology, and antidepressants, which are frequently used to treat chronic pain, especially that with a neuropathic component. Anti-epileptics are also used, particularly for excrutiating
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PMID:[Review of current pharmacologic treatment of pain]. 919 Mar 20


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