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Pain medicine: advances in basic sciences and clinical practice

2008; Elsevier BV; Volume: 101; Issue: 1 Linguagem: Inglês

10.1093/bja/aen120

1471-6771

Lesley Colvin, David G. Lambert,

Pain Management and Opioid Use

The meeting from which this issue stems celebrates advances made in ‘pain science’ translating to practice in man and the birth of The Faculty of Pain Medicine of The Royal College of Anaesthetists. With some imagination, it could be argued that the programme for a meeting such as this was set almost 350 yr ago by the philosopher and mathematician Rene’ Descartes who described human pain as ‘Fast moving particles of fire … the disturbance passes along the nerve filament until it reaches the brain … Descartes (1664).’ The 2008 meeting contained some excellent presentations covering: the sensing of pain (fast moving particles of fire), spinal processing/neuropathic pain (disturbance passes along the nerve filament), central processing (reaches the brain), and pain medicine/management (an extension of which Descartes would no doubt approve). Pain causes significant suffering and distress, is feared by patients, is often poorly understood, and hence poorly managed by clinicians. Acute pain is the most common reason for a medical consult and >50% of the population will make this consult during their life. A survey for The British Pain Society (2005) of 975 people reported that 21% experienced pain every day or most days. This equates to 10 million across GB!1British Pain Society GfK NOP Pain Survey.Available from www.britishpainsociety.orgDate: 2005Google Scholar In terms of chronic pain, the picture is not much better with figures for incidence of chronic pain being very variable. For example, in 1999, Elliott and colleagues2Elliott AM Smith BH Penny KI Smith WC Chambers WA The epidemiology of chronic pain in the community.Lancet. 1999; 354: 1248-1252Abstract Full Text Full Text PDF PubMed Scopus (943) Google Scholar surveyed 29 GP practices (3605 questionnaires covering 5036 patients) in the Grampian region of the UK and described an age-related increase in the self-reporting of chronic pain with an incidence of approximately one-third in 25–34 yr olds and a little less than two-thirds in those over 75 yr old. In March this year, Rivara and colleagues3Rivara FP MacKenzie EJ Jurkovich GJ Nathens AB Wang J Scharfstein DO Prevalence of pain in patients 1 year after major trauma.Arch Surg. 2008; 143: 282-287Crossref PubMed Scopus (117) Google Scholar surveyed more than 3000 trauma patients in 69 USA hospitals and found that ∼63% still reported pain 12 months after injury. Pain is one of the most common symptoms associated with cancer. The prevalence of cancer pain is approximately 30–50% among patients with cancer who are undergoing active treatment for a solid tumour and 70–90% among those with advanced disease.4Portenoy RK Lesage P Management of cancer pain.Lancet. 1999; 353: 1695-1700Abstract Full Text Full Text PDF PubMed Scopus (581) Google Scholar Eighty-eight per cent of cancer patients in the last year of their life are in pain and 47% of those treated for pain by their GPs said their treatment only partially controlled their pain.5Addington-Hall J McCarthy M Dying from cancer: results of a national population-based investigation.Ann Oncol. 1995; 9: 295-305Google Scholar Certain types of cancer pain can be particularly challenging to control, such as neuropathic pain and cancer-induced bone pain. Current treatments may have limited efficacy and there is a need for developing new strategies for managing cancer pain.6Colvin LA Fallon M Challenges in cancer pain management.Eur J Cancer. 2008; 8: 1083-1090Abstract Full Text Full Text PDF Scopus (81) Google Scholar, 7Colvin LA Forbes K Fallon MT Difficult cancer pain.Br Med J. 2006; 332: 1081-1083Crossref PubMed Scopus (24) Google Scholar, 8Delaney A Fleetwood-Walker S Colvin L Fallon M Translational medicine: cancer pain mechanisms and management.Br J Anaesth. 2008; 101: 87-94Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar Indeed, the use of nerve block in palliative care was discussed by Chambers.9Chambers WA Nerve blocks in palliative care.Br J Anaesth. 2008; 101: 95-100Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar Chronic pain, in particular, is a major socioeconomic drain. One example is chronic back pain that has been estimated to cost >£4 billion in terms of healthcare and social costs, including lost production costs.10Clinical Standards Advisory Group Epidemiology Review: The Epidemiology and Cost of Back Pain. 1994; 93Google Scholar A recent study of the prevalence of back pain in Germany found a life-time prevalence of 85.5% with 18.2% having severe pain.11Schmidt CO Raspe H Pfingsten M et al.Back pain in the German adult population: prevalence, severity, and sociodemographic correlates in a multiregional survey.Spine. 2007; 32: 2005-2011Crossref PubMed Scopus (279) Google Scholar Musculoskeletal pain in general is common, with ∼20% of people reporting widespread pain, and up to 50% reporting back pain in a 1 month period.12McBeth J Jones K Epidemiology of chronic musculoskeletal pain.Best Pract Res Clin Rheumatol. 2007; 21: 403-425Abstract Full Text Full Text PDF PubMed Scopus (429) Google Scholar Population factors such as education and socioeconomic variables and individual factors (smoking, diet, etc.) may all contribute to chronic musculoskeletal pain.11Schmidt CO Raspe H Pfingsten M et al.Back pain in the German adult population: prevalence, severity, and sociodemographic correlates in a multiregional survey.Spine. 2007; 32: 2005-2011Crossref PubMed Scopus (279) Google Scholar, 12McBeth J Jones K Epidemiology of chronic musculoskeletal pain.Best Pract Res Clin Rheumatol. 2007; 21: 403-425Abstract Full Text Full Text PDF PubMed Scopus (429) Google Scholar, 13Rubin DI Epidemiology and risk factors for spine pain.Neurol Clin. 2007; 25: 353-371Abstract Full Text Full Text PDF PubMed Scopus (464) Google Scholar Disappointingly, community-based psychosocial interventions, although superficially attractive, have not been of major benefit, although there are some examples of population-based interventions that may positively alter attitudes to back pain.14Morley S Eccleston C Williams A Systematic review and metaanalysis of randomized controlled trials of cognitive behaviour therapy and behaviour therapy for chronic pain in adults, excluding headache.Pain. 1999; 80: 1-13Abstract Full Text Full Text PDF PubMed Scopus (1240) Google Scholar, 15Buchbinder R Jolley D Population-based intervention to change back pain beliefs: three year follow up population survey.Br Med J. 2004; 328: 321-323Crossref PubMed Scopus (103) Google Scholar, 16United Kingdom Back Pain Exercise and Manipulation (UK BEAM) Trial Team UK BEAM randomised trial: effectiveness of physical treatments for back pain in primary care.Br Med J. 2004; 329: 1377-1381Crossref PubMed Scopus (434) Google Scholar, 17Scholten-Peeters GG Neeleman-van der Steen CW van der Windt DA Hendriks EJ Verhagen AP Oostendorp RA Education by general practitioners or education and exercises by physiotherapists for patients with whiplash-associated disorders? A randomized clinical trial.Spine. 2006; 31: 723-731Crossref PubMed Scopus (61) Google Scholar Neuropathic pain, which is particularly challenging to treat effectively, is found in similar patient groups as those affected by back pain, with a prevalence of ∼8%.18Torrance N Smith BH Bennett MI et al.The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey.J Pain. 2006; 7: 281-289Abstract Full Text Full Text PDF PubMed Scopus (731) Google Scholar It is clear that we need to improve our understanding of modifiable risk factors that predispose to developing chronic pain, in order that we can structure our services to prevent chronic pain developing or target it early in its course.19Smith BH Macfarlane GJ Torrance N Smith BH Macfarlane GJ Torrance N Epidemiology of chronic pain, from the laboratory to the bus stop: time to add understanding of biological mechanisms to the study of risk factors in population-based research?.Pain. 2007; 127: 5-10Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar 20Macfarlane GJ Looking back: developments in our understanding of the occurrence, aetiology and prognosis of chronic pain 1954–2004.Rheumatology. 2005; 44: v23-v26Crossref Scopus (10) Google Scholar Adequate and appropriate pain assessment in the clinic is an important prerequisite in formulating a pain management plan, although there is considerable evidence that this is often not done outside the specialist setting.21Von Roenn JH Cleeland CS Gonin R Hatfield AK Pandya KJ Physician attitudes and practice in cancer pain management.Ann Intern Med. 1993; 119: 121-126Crossref PubMed Scopus (721) Google Scholar 22Wallace K Reed B Pasero C et al.Staff nurses’ perceptions of barriers to effective pain management.J Pain Symptom Manage. 1995; 10: 204-213Abstract Full Text PDF PubMed Scopus (25) Google Scholar Both the importance of pain assessment tools and their role in designing clinical trials are reviewed by Breivik and colleagues23Breivik H Borchgrevink PC Allen SM et al.Assessment of pain.Br J Anaesth. 2008; 101: 17-24Abstract Full Text Full Text PDF PubMed Scopus (1112) Google Scholar in this issue. Also of relevance in assessing any analgesic is the design of the trial—in particular, the techniques for comparing efficacy of analgesics. Both Breivik and colleagues23Breivik H Borchgrevink PC Allen SM et al.Assessment of pain.Br J Anaesth. 2008; 101: 17-24Abstract Full Text Full Text PDF PubMed Scopus (1112) Google Scholar and McQuay and colleagues24McQuay HJ Poon KH Derry S Moore RA Acute pain: combination treatments and how we measure their efficacy.Br J Anaesth. 2008; 101: 69-76Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar discuss the potential erroneous conclusions that may be reached by such problems in trial design. The importance of psychological factors in the development of chronic pain cannot be underestimated. In his lecture, Prof. Morley25Morley S Psychology of pain.Br J Anaesth. 2008; 101: 25-31Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar elegantly discussed the dynamic processes that lead to psychological morbidity, with pain interrupting normal function and interaction with other people. This leads to interference and development of fear-avoidance, culminating in loss of identity.26Vlaeyen JWS Morley S Active despite pain: the putative role of stop-rules and current mood.Pain. 2004; 110: 512-516Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar, 27Morley S Davies C Barton S Possible selves in chronic pain: self-pain enmeshment, adjustment and acceptance.Pain. 2005; 115: 84-94Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar, 28Chapman CR Gavrin J Suffering: the contributions of persistent pain.Lancet. 1999; 353: 2233-2237Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar Since the seminal description of the spinal gate control theory for pain by Melzack and Wall,29Melzack R Wall PD Pain mechanisms: a new theory.Science. 1965; 150: 971-979Crossref PubMed Scopus (7280) Google Scholar the spinal cord has remained a core target in blocking nociceptive transmission and, as indicated in D’Mello and Dickenson,30D’Mello R Dickenson AH Spinal cord mechanisms of pain.Br J Anaesth. 2008; 101: 8-16Abstract Full Text Full Text PDF PubMed Scopus (323) Google Scholar is a rich source of potential novel targets for, in particular, chronic pain. Linking our understanding of the neurobiology of pain with the clinical setting has been significantly advanced by modern neuroimaging techniques, as exemplified in the Pat Wall Lecture, given by Prof. Tracey.31Tracey I Imaging pain.Br J Anaesth. 2008; 101: 32-39Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar She introduced the fascinating concept of chronic pain being not just a symptom, but also a neurodegenerative disorder with long-term consequences.32Tracey I Mantyh PW The cerebral signature for pain perception and its modulation.Neuron. 2007; 55: 377-391Abstract Full Text Full Text PDF PubMed Scopus (1191) Google Scholar 33Sud R Ignatowski TA Lo CP et al.Uncovering molecular elements of brain–body communication during development and treatment of neuropathic pain.Brain Behav Immun. 2007; 21: 112-124Crossref PubMed Scopus (15) Google Scholar The potential role of functional magnetic imaging in teasing out the different aspects of pain perception may have major implications in developing new therapies.34Wise RG Tracey I The role of fMRI in drug discovery.J Magn Reson Imaging. 2006; 23: 862-876Crossref PubMed Scopus (165) Google Scholar, 35Bantick SJ Wise RG Ploghaus A Clare S Smith SM Tracey I Imaging how attention modulates pain in humans using functional MRI.Brain. 2002; 125: 310-319Crossref PubMed Scopus (651) Google Scholar, 36Longe SE Wise R Bantick S et al.Counter-stimulatory effects on pain perception and processing are significantly altered by attention: an fMRI study.Neuroreport. 2001; 12: 2021-2025Crossref PubMed Scopus (90) Google Scholar, 37Ploghaus A Tracey I Gati JS et al.Dissociating pain from its anticipation in the human brain.Science. 1999; 284: 1979-1981Crossref PubMed Scopus (911) Google Scholar It is exactly 10 yr since the British Journal of Anaesthesia published a post-graduate issue entitled ‘Recent advances in opioid pharmacology’38Lambert DG, ed. British Journal of Anaesthesia 1998 Postgraduate Issue ‘Recent Advances in Opioid Pharmacology’ Vol. 81 No. 1, Cambridge, UK: Professional and Scientific Publications.Google Scholar where the cloning of the classical (μ-MOP, δ-DOP, and κ-KOP) and non-classical (Nociceptin/Orphanin FQ-NOP) opioid receptors were reviewed adding a new sense of vigour to pain-related research. From a basic sciences perspective, the intervening decade has seen some fascinating developments and several new drugs reaching the clinic including gabapentin/pregabalin,39Dooley DJ Taylor CP Donevan S Feltner D Ca2+ channel alpha 2delta ligands: novel modulators of neurotransmission.Trends Pharmacol Sci. 2007; 28: 75-82Abstract Full Text Full Text PDF PubMed Scopus (330) Google Scholar 40Gilron I Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions.Curr Opin Anaesthesiol. 2007; 20: 456-472Crossref PubMed Scopus (184) Google Scholar these were described and added to the bigger picture of a relatively advanced pharmaceutical pipeline for neuropathic pain by Dray.41Dray A Neuropathic pain: emerging treatments.Br J Anaesth. 2008; 101: 48-58Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar There have also been several advances in the understanding of the wider (non-Na-channel) effects of local anaesthetics in the periphery and spinal cord42Strichartz GR Novel ideas of local anaesthetic actions on various ion channels to ameliorate postoperative pain.Br J Anaesth. 2008; 101: 45-47Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar and Hosking and Zajicek43Hosking RD Zajicek JP Therapeutic potential of cannabis in pain medicine.Br J Anaesth. 2008; 101: 59-68Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar covered the exciting new information on the use of cannabis in pain. The group of Prof. Stein44Stein C Schäfer M Machelska H Attacking pain at its source: new perspectives on opioids.Nat Med. 2003; 9: 1003-1008Crossref PubMed Scopus (482) Google Scholar 45Rittner HL Brack A Stein C Pain and the immune system.Br J Anaesth. 2008; 101: 40-44Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar in Berlin have described a neuroimmune axis in which peripheral inflammation up-regulates opioid receptors on peripheral nerves at the inflammatory site and infiltrating white cells release opioid peptides to activate these receptors and produce a degree of peripheral analgesia. So what for the next decade? New opioids with reduced side-effect profiles; like tolerance? New non-opioid-based therapies? Understanding the genetics of pain and using genomic technology to provide patients with individually tailored therapy? Perhaps the link between acute and chronic pain is most apparent when studying persistent post-surgical pain. The evidence for this actually being a significant problem has been around for some time now,46Macrae WA Davies HTO Chronic postsurgical pain.in: Crombie IK Epidemiology of Pain. IASP, Seattle, WA1999: 125-142Google Scholar 47Macrae WA Chronic pain after surgery.Br J Anaesth. 2001; 87: 88-98Abstract Full Text Full Text PDF PubMed Scopus (530) Google Scholar but it remains a significant clinical problem, which is not yet fully understood. What is clear is that the one definite risk factor for developing this challenging chronic pain syndrome is surgery—and perhaps the need for any surgical intervention requires more careful evaluation.48Macrae WA Chronic post-surgical pain: 10 years on.Br J Anaesth. 2008; 101: 77-86Abstract Full Text Full Text PDF PubMed Scopus (658) Google Scholar Pain in particular subgroups, ranging from children to the elderly, may need a more specialized approach or support for non-specialists. The plasticity of the nervous system at birth and in early years is in contrast to the constrained ability of elderly patients to respond to pain and analgesia.49Walker SM Pain in children: recent advances and ongoing challenges.Br J Anaesth. 2008; 101: 101-110Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar 50Karp JF Shega JW Morone NE Weiner DK Advances in understanding the mechanisms and management of persistent pain in older adults.Br J Anaesth. 2008; 101: 111-120Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar In veterinary practice, there may be some lag time before clinical practice changes, but at least pain is now acknowledged to be a problem not only in companion animals, but also in laboratory and agricultural settings. Once again, as in the human setting, basic assessment of pain remains a problem.51Flecknell P Analgesia from a veterinary perspective.Br J Anaesth. 2008; 101: 121-124Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar The menace of chronic pain continues to evade effective and reproducible treatment. Pain medicine may be one of the areas of medicine where true translational research may yield direct clinical benefits to patients in the near future.52Black N The Cooksey review of UK health research funding.Br Med J. 2006; 333: 1231-1232Crossref PubMed Scopus (19) Google Scholar 53Mao J Translational pain research: bridging the gap between basic and clinical research.Pain. 2002; 97: 183-187Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar This may be achieved by interplay between those in the laboratory and members of the new Faculty of Pain Medicine in the clinic.