- Email: [email protected]
Goddess lanced through the hart
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Schulze S, Roikjaer O, Hasselstrom L, Jensen NH, Kehlet H. Epidura bupivacaine and morphine plus systemic indomethacin eliminates pain but not systemic response and convalescence after cholecystectomy. Surgery 1988; 103: 321-27. Anand KJS, Hickey PR. Halothane-morphine compared with high dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl K Med 1992; 326: 1-9. Rogers MC. Do the right thing: pain relief in infants and children. N Engl J Med 1992; 326: 55-56. Arnold JH, Truog RD, Orav EJ, Scavone JM, Hershenson MB. Tolerance and dependance in neonates sedated with fentanyl during extracorporeal membrane oxygenation. Anesthesiology 1990; 73: 1136-40.
7
Greeley WJ, deBruijn NP. Changes in sufentanil pharmacokinetics within the neonatal period. Anesth Analg 1988; 67: 86-90.
Peripheral analgesia See page 321
A greater insight into the processes of nociception has been leading to the development of increasingly varied approaches to drug administration for the management of acute pain. Evidence from animal models of inflammation suggests enhanced antinociceptive activity of endogenous peptides and exogenous opioid agonists via an action at peripheral opioid receptors on primary afferent neurons.1
Furthermore, enkephalinase (endopeptidase 24.11), an enzyme capable of cleaving neuropeptides and immune mediators such as substance P and enkephalins, has been found in the synovial fluid.2 The occurrence of enkephalinase is correlated with the numbers of polymorphonuclear cells and lymphocytes. The role of this peptidase in the synovial fluid may be to control the local peptide concentration and thereby its degree of receptor interaction within the joint. Enkephalinase could thus reflect the intensity of the inflammatory process-or represent a physiological regulator of both pain and inflammation.2 Taken together, these data suggest possible analgesic effects of opioids administered in the vicinity of peripheral sensory nerve terminals in the synovium.3 In this issue, Stein and colleagues provide further support for the concept of peripheral opioid analgesia and document endogenous opioid peptides in human inflamed synovial tissue. They also suggest the existence of a "peripheral gate" in addition to spinal mechanisms of pain control. If such a gate were to be confirmed it might be possible to manipulate the physiological processes of pain signal transduction, transmission, and modulation by interventions at discrete levels by highly specific drugs. There would be a huge potential for novel peripheral analgesics, such as peripherally acting opioids, which do not cross the blood/brain barrier, and enkephalinase inhibitors. Such agents could be used in multimodal regimens to modify the injury response and prevent pain. Well-controlled clinical studies showing peripheral opioid analgesia are few and controversial. Intra-articular
320
-’-:-.
morphine after knee arthroscopy has been shown to provide effective and long-lasting pain relief.4 The analgesia seems to result from a local action because the plasma concentrations of morphine and its major metabolties were clinically insignificant.5 Although opioid receptors have been found in synovial tissue the receptor type is unknown.5 Future studies of the intra-articular technique should take into account the dose and volume of the injected drug and the effect of tourniquets, and preoperative intra-articular inflammation should be correlated with postoperative pain relief. In addition, it would be interesting to know if the intra-articular injection of local anaesthetics, non-steroidal anti-inflammatory drugs, and Ct2-agonists, alone or in combination with opioid agonists, is of any therapeutic value. If further clinical studies do clarify the issues raised by experimental work, clinicians may be able to tackle postoperative pain by a combination of "peripheral", "balanced", and "pre-emptive" analgesia. Girish P Joshi Department of Anesthesiology and Pain Management, Southwestern Medical Center at Dallas, Texas, USA 1 2
3
4
5
Basbaum AI, Levine JD. Opiate analgesia: how central is a peripheral target? N Engl J Med 1991; 325: 1168-69. Appelboom T, DeMaetelaer V, DePrez E, Hauzeur J-P, DeschodtLanchkman M. Enkephalinase: a physiologic neuroimmunomodulator detected in the synovial fluid. Arthritis Rheum 1991 34: 1048-51. Bjurholm A, Kreicbergs A, Ahmed A, Schltzberg M. Nonadrenergic and peptidergic nerves in the synovial membrane of the SpragueDawley rat. Arthritis Rheum 1990; 33: 859-65. Joshi GP, McCarroll SM, O’Brien TM, Lenane P. Intra-articular analgesia following knee arthroscopy. Anesth Analg 1993; 76: 333-36. Lawrence AJ, Joshi GP, Michalkiewicz B, Blunnie WP, Moriarty DC. Evidence for analgesia mediated by peripheral opioid receptors in inflamed synovial tissue. Eur J Clin Pharmacol 1992; 43: 351-55.
Goddess lanced
through the hart
Grown men and women who should have known better plus elastic youth met up last Wednesday in a Hampstead dell for a ritual. The hosts (the BM]) chose to play in a pentacle but the magic soon wore off and, with dusk and mosquitoes gathering, they drowned their sorrows in a nearby pond. The victors (The Lancet) took a look. Muttering Weil’s disease and Crocodile Dundee and heeding the rumour that the opposing captain had no swimming trunks they repaired with the remnants of the opposition to Zimorski’s. From BMA House have lately emerged stern declarations on exercise (good) and alcohol (bad) but the BM] had only one bicycle and did not pass up on the vodka, alarmingly and aptly named "bison". This piece of nonsense about a softball match may sound more suited to In England Now but that column, after half a century, has changed its clothes (see p 363) and, happily for its future, was full this month. some
David Sharp The Lancet, London, UK
4
5 6
Schulze S, Roikjaer O, Hasselstrom L, Jensen NH, Kehlet H. Epidura bupivacaine and morphine plus systemic indomethacin eliminates pain but not systemic response and convalescence after cholecystectomy. Surgery 1988; 103: 321-27. Anand KJS, Hickey PR. Halothane-morphine compared with high dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl K Med 1992; 326: 1-9. Rogers MC. Do the right thing: pain relief in infants and children. N Engl J Med 1992; 326: 55-56. Arnold JH, Truog RD, Orav EJ, Scavone JM, Hershenson MB. Tolerance and dependance in neonates sedated with fentanyl during extracorporeal membrane oxygenation. Anesthesiology 1990; 73: 1136-40.
7
Greeley WJ, deBruijn NP. Changes in sufentanil pharmacokinetics within the neonatal period. Anesth Analg 1988; 67: 86-90.
Peripheral analgesia See page 321
A greater insight into the processes of nociception has been leading to the development of increasingly varied approaches to drug administration for the management of acute pain. Evidence from animal models of inflammation suggests enhanced antinociceptive activity of endogenous peptides and exogenous opioid agonists via an action at peripheral opioid receptors on primary afferent neurons.1
Furthermore, enkephalinase (endopeptidase 24.11), an enzyme capable of cleaving neuropeptides and immune mediators such as substance P and enkephalins, has been found in the synovial fluid.2 The occurrence of enkephalinase is correlated with the numbers of polymorphonuclear cells and lymphocytes. The role of this peptidase in the synovial fluid may be to control the local peptide concentration and thereby its degree of receptor interaction within the joint. Enkephalinase could thus reflect the intensity of the inflammatory process-or represent a physiological regulator of both pain and inflammation.2 Taken together, these data suggest possible analgesic effects of opioids administered in the vicinity of peripheral sensory nerve terminals in the synovium.3 In this issue, Stein and colleagues provide further support for the concept of peripheral opioid analgesia and document endogenous opioid peptides in human inflamed synovial tissue. They also suggest the existence of a "peripheral gate" in addition to spinal mechanisms of pain control. If such a gate were to be confirmed it might be possible to manipulate the physiological processes of pain signal transduction, transmission, and modulation by interventions at discrete levels by highly specific drugs. There would be a huge potential for novel peripheral analgesics, such as peripherally acting opioids, which do not cross the blood/brain barrier, and enkephalinase inhibitors. Such agents could be used in multimodal regimens to modify the injury response and prevent pain. Well-controlled clinical studies showing peripheral opioid analgesia are few and controversial. Intra-articular
320
-’-:-.
morphine after knee arthroscopy has been shown to provide effective and long-lasting pain relief.4 The analgesia seems to result from a local action because the plasma concentrations of morphine and its major metabolties were clinically insignificant.5 Although opioid receptors have been found in synovial tissue the receptor type is unknown.5 Future studies of the intra-articular technique should take into account the dose and volume of the injected drug and the effect of tourniquets, and preoperative intra-articular inflammation should be correlated with postoperative pain relief. In addition, it would be interesting to know if the intra-articular injection of local anaesthetics, non-steroidal anti-inflammatory drugs, and Ct2-agonists, alone or in combination with opioid agonists, is of any therapeutic value. If further clinical studies do clarify the issues raised by experimental work, clinicians may be able to tackle postoperative pain by a combination of "peripheral", "balanced", and "pre-emptive" analgesia. Girish P Joshi Department of Anesthesiology and Pain Management, Southwestern Medical Center at Dallas, Texas, USA 1 2
3
4
5
Basbaum AI, Levine JD. Opiate analgesia: how central is a peripheral target? N Engl J Med 1991; 325: 1168-69. Appelboom T, DeMaetelaer V, DePrez E, Hauzeur J-P, DeschodtLanchkman M. Enkephalinase: a physiologic neuroimmunomodulator detected in the synovial fluid. Arthritis Rheum 1991 34: 1048-51. Bjurholm A, Kreicbergs A, Ahmed A, Schltzberg M. Nonadrenergic and peptidergic nerves in the synovial membrane of the SpragueDawley rat. Arthritis Rheum 1990; 33: 859-65. Joshi GP, McCarroll SM, O’Brien TM, Lenane P. Intra-articular analgesia following knee arthroscopy. Anesth Analg 1993; 76: 333-36. Lawrence AJ, Joshi GP, Michalkiewicz B, Blunnie WP, Moriarty DC. Evidence for analgesia mediated by peripheral opioid receptors in inflamed synovial tissue. Eur J Clin Pharmacol 1992; 43: 351-55.
Goddess lanced
through the hart
Grown men and women who should have known better plus elastic youth met up last Wednesday in a Hampstead dell for a ritual. The hosts (the BM]) chose to play in a pentacle but the magic soon wore off and, with dusk and mosquitoes gathering, they drowned their sorrows in a nearby pond. The victors (The Lancet) took a look. Muttering Weil’s disease and Crocodile Dundee and heeding the rumour that the opposing captain had no swimming trunks they repaired with the remnants of the opposition to Zimorski’s. From BMA House have lately emerged stern declarations on exercise (good) and alcohol (bad) but the BM] had only one bicycle and did not pass up on the vodka, alarmingly and aptly named "bison". This piece of nonsense about a softball match may sound more suited to In England Now but that column, after half a century, has changed its clothes (see p 363) and, happily for its future, was full this month. some
David Sharp The Lancet, London, UK