Pain medicine: advances in basic sciences and clinical practice
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!1 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 colleagues2 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 colleagues3 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.4 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.5 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.6–8 Indeed, the use of nerve block in palliative care was discussed by Chambers.9
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.10 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.11 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.12 Population factors such as education and socioeconomic variables and individual factors (smoking, diet, etc.) may all contribute to chronic musculoskeletal pain.11–13 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.14–17 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%.18 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.19 20
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.21 22 Both the importance of pain assessment tools and their role in designing clinical trials are reviewed by Breivik and colleagues23 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 colleagues23 and McQuay and colleagues24 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. Morley25 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.26–28
Since the seminal description of the spinal gate control theory for pain by Melzack and Wall,29 the spinal cord has remained a core target in blocking nociceptive transmission and, as indicated in D'Mello and Dickenson,30 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.31 She introduced the fascinating concept of chronic pain being not just a symptom, but also a neurodegenerative disorder with long-term consequences.32 33 The potential role of functional magnetic imaging in teasing out the different aspects of pain perception may have major implications in developing new therapies.34–37
It is exactly 10 yr since the British Journal of Anaesthesia published a post-graduate issue entitled ‘Recent advances in opioid pharmacology’38 where the cloning of the classical (µ-MOP, 
-DOP, and 
-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,39 40 these were described and added to the bigger picture of a relatively advanced pharmaceutical pipeline for neuropathic pain by Dray.41 There have also been several advances in the understanding of the wider (non-Na-channel) effects of local anaesthetics in the periphery and spinal cord42 and Hosking and Zajicek43 covered the exciting new information on the use of cannabis in pain. The group of Prof. Stein44 45 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,46 47 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.48 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.49 50 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.51
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.52 53 This may be achieved by interplay between those in the laboratory and members of the new Faculty of Pain Medicine in the clinic.
1 Department of Anaesthesia, Critical Care and Pain Medicine
University of Edinburgh
Western General Hospital
Crewe Road Edinburgh EH4 2XU UK
2 Department of Cardiovascular Sciences (Pharmacology and Therapeutics Group)
Division of Anaesthesia Critical Care and Pain Management
University of Leicester
Leicester Royal Infirmary Leicester LE1 5WW UK
* E-mail: dgl3{at}le.ac.uk
References
1 British Pain Society. GfK NOP Pain Survey (2005) Available from www.britishpainsociety.org.
2 Elliott AM, Smith BH, Penny KI, Smith WC, Chambers WA. The epidemiology of chronic pain in the community. Lancet (1999) 354:1248–52.[CrossRef][Web of Science][Medline]
3 Rivara FP, MacKenzie EJ, Jurkovich GJ, Nathens AB, Wang J, Scharfstein DO. Prevalence of pain in patients 1 year after major trauma. Arch Surg (2008) 143:282–7.
4 Portenoy RK, Lesage P. Management of cancer pain. Lancet (1999) 353:1695–700.[CrossRef][Web of Science][Medline]
5 Addington-Hall J, McCarthy M. Dying from cancer: results of a national population-based investigation. Ann Oncol (1995) 9:295–305.
6 Colvin LA, Fallon M. Challenges in cancer pain management. Eur J Cancer (2008) 8:1083–90.
7 Colvin LA, Forbes K, Fallon MT. Difficult cancer pain. Br Med J (2006) 332:1081–3.
8 Delaney A, Fleetwood-Walker S, Colvin L, Fallon M. Translational medicine: cancer pain mechanisms and management. Br J Anaesth (2008) 101:87–94.
9 Chambers WA. Nerve blocks in palliative care. Br J Anaesth (2008) 101:95–100.
10 Clinical Standards Advisory Group. Epidemiology Review: The Epidemiology and Cost of Back Pain (1994) 93.
11 Schmidt 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) 32:2005–11.[CrossRef][Web of Science][Medline]
12 McBeth J, Jones K. Epidemiology of chronic musculoskeletal pain. Best Pract Res Clin Rheumatol (2007) 21:403–25.[CrossRef][Medline]
13 Rubin DI. Epidemiology and risk factors for spine pain. Neurol Clin (2007) 25:353–71.[CrossRef][Web of Science][Medline]
14 Morley 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) 80:1–13.[CrossRef][Web of Science][Medline]
15 Buchbinder R, Jolley D. Population-based intervention to change back pain beliefs: three year follow up population survey. Br Med J (2004) 328:321–3.
16 United 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) 329:1377–81.
17 Scholten-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) 31:723–31.[CrossRef][Web of Science][Medline]
18 Torrance 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) 7:281–9.[CrossRef][Web of Science][Medline]
19 Smith 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) 127:5–10.[CrossRef][Web of Science][Medline]
20 Macfarlane GJ. Looking back: developments in our understanding of the occurrence, aetiology and prognosis of chronic pain 1954–2004. Rheumatology (2005) 44(Suppl. 4):v23–6.[CrossRef]
21 Von Roenn JH, Cleeland CS, Gonin R, Hatfield AK, Pandya KJ. Physician attitudes and practice in cancer pain management. Ann Intern Med (1993) 119:121–6.
22 Wallace K, Reed B, Pasero C, et al. Staff nurses' perceptions of barriers to effective pain management. J Pain Symptom Manage (1995) 10:204–13.[CrossRef][Web of Science][Medline]
23 Breivik H, Borchgrevink PC, Allen SM, et al. Assessment of pain. Br J Anaesth (2008) 101:17–24.
24 McQuay HJ, Poon KH, Derry S, Moore RA. Acute pain: combination treatments and how we measure their efficacy. Br J Anaesth (2008) 101:69–76.
25 Morley S. Psychology of pain. Br J Anaesth (2008) 101:25–31.
26 Vlaeyen JWS, Morley S. Active despite pain: the putative role of stop-rules and current mood. Pain (2004) 110:512–6.[CrossRef][Web of Science][Medline]
27 Morley S, Davies C, Barton S. Possible selves in chronic pain: self-pain enmeshment, adjustment and acceptance. Pain (2005) 115:84–94.[CrossRef][Web of Science][Medline]
28 Chapman CR, Gavrin J. Suffering: the contributions of persistent pain. Lancet (1999) 353:2233–7.[CrossRef][Web of Science][Medline]
29 Melzack R, Wall PD. Pain mechanisms: a new theory. Science (1965) 150:971–9.
30 D'Mello R, Dickenson AH. Spinal cord mechanisms of pain. Br J Anaesth (2008) 101:8–16.
31 Tracey I. Imaging pain. Br J Anaesth (2008) (101):32–9.
32 Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron (2007) 55:377–91.[CrossRef][Web of Science][Medline]
33 Sud 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) 21:112–24.[CrossRef][Web of Science][Medline]
34 Wise RG, Tracey I. The role of fMRI in drug discovery. J Magn Reson Imaging (2006) 23:862–76.[CrossRef][Web of Science][Medline]
35 Bantick SJ, Wise RG, Ploghaus A, Clare S, Smith SM, Tracey I. Imaging how attention modulates pain in humans using functional MRI. Brain (2002) 125:310–9.
36 Longe 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) 12:2021–5.[CrossRef][Web of Science][Medline]
37 Ploghaus A, Tracey I, Gati JS, et al. Dissociating pain from its anticipation in the human brain. Science (1999) 284:1979–81.
38 Lambert DG. British Journal of Anaesthesia 1998 Postgraduate Issue ‘Recent Advances in Opioid Pharmacology’. Vol. 81(No. 1). Cambridge, UK: Professional and Scientific Publications.
39 Dooley DJ, Taylor CP, Donevan S, Feltner D. Ca2+ channel alpha 2delta ligands: novel modulators of neurotransmission. Trends Pharmacol Sci (2007) 28:75–82.[CrossRef][Medline]
40 Gilron I. Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions. Curr Opin Anaesthesiol (2007) 20:456–72.[Medline]
41 Dray A. Neuropathic pain: emerging treatments. Br J Anaesth (2008) 101:48–58.
42 Strichartz GR. Novel ideas of local anaesthetic actions on various ion channels to ameliorate postoperative pain. Br J Anaesth (2008) 101:45–7.
43 Hosking RD, Zajicek JP. Therapeutic potential of cannabis in pain medicine. Br J Anaesth (2008) 101:59–68.
44 Stein C, Schäfer M, Machelska H. Attacking pain at its source: new perspectives on opioids. Nat Med (2003) 9:1003–8.[CrossRef][Web of Science][Medline]
45 Rittner HL, Brack A, Stein C. Pain and the immune system. Br J Anaesth (2008) 101:40–4.
46 Macrae WA, Davies HTO. Chronic postsurgical pain. Epidemiology of Pain—Crombie IK, ed. (1999) Seattle, WA: IASP. 125–42.
47 Macrae WA. Chronic pain after surgery. Br J Anaesth (2001) 87:88–98.
48 Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth (2008) 101:77–86.
49 Walker SM. Pain in children: recent advances and ongoing challenges. Br J Anaesth (2008) 101:101–10.
50 Karp JF, Shega JW, Morone NE, Weiner DK. Advances in understanding the mechanisms and management of persistent pain in older adults. Br J Anaesth (2008) 101:111–20.
51 Flecknell P. Analgesia from a veterinary perspective. Br J Anaesth (2008) 101:121–4.
52 Black N. The Cooksey review of UK health research funding. Br Med J (2006) 333:1231–2.
53 Mao J. Translational pain research: bridging the gap between basic and clinical research. Pain (2002) 97:183–7.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. M. Hopkins and J. G. Hardman Advances in pharmacology and therapeutics Br. J. Anaesth., July 1, 2009; 103(1): 1 - 2. [Full Text] [PDF]
|
|
|
|
|
|
N. Dietis, R. Guerrini, G. Calo, S. Salvadori, D. J. Rowbotham, and D. G. Lambert Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile Br. J. Anaesth., July 1, 2009; 103(1): 38 - 49. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||