British Journal of Anaesthesia - current issue

Pain medicine: advances in basic sciences and clinical practice

Colvin, L. A., Lambert, D. G. — 2008-06-13

The Faculty of Pain Medicine of the Royal College of Anaesthetists

Justins, D. M. — 2008-06-13

Spinal cord mechanisms of pain

D'Mello, R., Dickenson, A. H. — 2008-06-13

The spinal cord is the first relay site in the transmission of nociceptive information from the periphery to the brain. Sensory signals are transmitted from the periphery by primary afferent fibres into the dorsal horn of the spinal cord, where these afferents synapse with intrinsic spinal dorsal horn neurones. Spinal projection neurones then convey this information to higher centres in the brain, where non-noxious and noxious signals can be perceived. During nociceptive transmission, the output of the spinal cord is dependent on various spinal mechanisms which can either increase or decrease the activity of dorsal horn neurones. Such mechanisms include local excitatory and inhibitory interneurones, N-methyl-d-aspartate receptor activation, and descending influences from the brainstem, which can be both inhibitory and excitatory in nature. After nerve injury or conditions of inflammation, shifts can occur in these excitatory and inhibitory mechanisms which modulate spinal excitability, often resulting in the heightened response of dorsal neurones to incoming afferent signals, and increased output to the brain, a phenomenon known as central sensitization. In this review, we consider the ways in which spinal cord activity may be altered in chronic pain states. In addition, we discuss the spinal mechanisms which are targeted by current analgesics used in the management of chronic pain.

Assessment of pain

2008-06-13

Valid and reliable assessment of pain is essential for both clinical trials and effective pain management. The nature of pain makes objective measurement impossible. Acute pain can be reliably assessed, both at rest (important for comfort) and during movement (important for function and risk of postoperative complications), with one-dimensional tools such as numeric rating scales or visual analogue scales. Both these are more powerful in detecting changes in pain intensity than a verbal categorical rating scale. In acute pain trials, assessment of baseline pain must ensure sufficient pain intensity for the trial to detect meaningful treatment effects. Chronic pain assessment and its impact on physical, emotional, and social functions require multidimensional qualitative tools and health-related quality of life instruments. Several disease- and patient-specific functional scales are useful, such as the Western Ontario and MacMaster Universities for osteoarthritis, and several neuropathic pain screening tools. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations for outcome measurements of chronic pain trials are also useful for routine assessment. Cancer pain assessment is complicated by a number of other bodily and mental symptoms such as fatigue and depression, all affecting quality of life. It is noteworthy that quality of life reported by chronic pain patients can be as much affected as that of terminal cancer patients. Any assessment of pain must take into account other factors, such as cognitive impairment or dementia, and assessment tools validated in the specific patient groups being studied.

Psychology of pain

Morley, S. — 2008-06-13

This article briefly reviews psychological aspects of pain, paying special attention to chronic pain. The review considers the interruptive and interference effects of pain and its impact on a person's identity. The importance of processes related to interruption, interference, and identity will vary across people and the duration of pain. Although brief phasic pain such as that presented in the laboratory will have marked interruptive effects, it is unlikely to produce interference or impact on a person's identity. Acute clinical pain will have both interruptive and interference effects, albeit of a temporary nature, but it is unlikely to have any impact on a person's identity. Chronic persistent pain or frequent recurrent episodic pain, such as headache, may have profound effects on a Person's life. Each of these themes is illustrated with examples drawn from the experimental and clinical literature.

Imaging pain

Tracey, I. — 2008-06-13

Pain that persists or recurs for more than 3 months is defined as chronic and as such is one of the largest medical health problems in the developed world. Although the management and treatment of acute pain is reasonably good, the needs of chronic pain patients are largely unmet, creating an enormous emotional and financial burden to sufferers, carers, and society. Improvements in our ability to diagnose the causes of chronic pain are desperately needed. Furthermore, the pharmaceutical industry is struggling to find new and better drugs to treat chronic pain sufferers. Innovative methods that can aid decisions regarding choice and targeting of treatments alongside conventional clinical measures are therefore needed. Neuroimaging methods have the capacity to fulfil this need as they provide a non-invasive, systems-level understanding of the central mechanisms involved in pain processing. To date, the focus has been to dissect the physiological, psychological, and cognitive factors that influence nociceptive inputs to alter pain perception in healthy subjects and patients suffering from chronic pain. Obtaining reliable objective information related to the individual’s subjective pain experience provides a powerful means of understanding not only the central mechanisms contributing to the chronicity of pain states but also the potential diagnostic information. Identifying non-invasively where plasticity, sensitization and other amplification processes might occur along the pain neuraxis for an individual and relating this to their specific pain experience or measure of pain relief is therefore of considerable interest to the clinical pain community and pharmaceutical industry. In this review, I shall briefly summarize our current state of knowledge regarding the central representation of pain perception in varying situations.

Pain and the immune system

Rittner, H. L., Brack, A., Stein, C. — 2008-06-13

In inflammation, leucocytes containing opioid peptides migrate into the tissue. Opioid peptides can be released and bind to opioid receptors on peripheral nerve terminals, which counteracts inflammatory pain. Migration of opioid peptide-containing leucocytes is controlled by chemokines and adhesion molecules. Neurokinins, such as, substance P also contribute to the recruitment of these cells. Opioid peptide release from granulocytes can be stimulated by chemokines, such as, CXCR2 ligands. The release is dependent on intracellular calcium and activation of phosphoinositol-3 kinase and p38 mitogen activated kinase. Endogenous opioid peptides produced by leucocytes not only confer analgesia but recent evidence supports the concept that they also prevent the development of tolerance at peripheral opioid receptors. This review presents the discoveries that led to the concept of analgesia produced by immune-derived opioids.

Novel ideas of local anaesthetic actions on various ion channels to ameliorate postoperative pain

Strichartz, G. R. — 2008-06-13

This review considers the ion channels that underlie transduction of nociceptive energies in the periphery, that are involved in impulse initiation and propagation in peripheral sensory neurones, and that participate in pre- and post-synaptic actions in the spinal cord dorsal horn, in light of their susceptibility to local anaesthetics. Although there are results from experiments on isolated cells and tissues ex vivo that support the hypothesized actions, their extrapolation to actions in vivo and the consequences for peri- and postoperative pain control are largely speculative.

Neuropathic pain: emerging treatments

Dray, A. — 2008-06-13

Neuropathic pain remains one of the most challenging of all neurological diseases and presents a large unmet need for improved therapies. Many mechanistic details are still lacking, but greater knowledge of overlapping mechanisms and disease comorbidities has highlighted key areas for intervention. These include peripheral and central hyperexcitability. Among the molecular drivers are ion channels (Nav1.7, Nav1.8, Nav1.3, Cav2.2, and alpha2-delta subunits) whose expression is changed during neuropathic pain and their block shows therapeutic utility. Block of a number of ligand-gated channels [transient receptor potential (TRP)V1, TRPM8, and neuronal nicotinic receptors (NNRs)], important in neural sensitization, may also prove beneficial. Other approaches, such as the modulation of peripheral excitability via CB1 receptors, reduction of spinal excitability through block of glutamate receptors (metabotropic glutamate receptor 5 and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate), block of activated spinal neuroglial (CCR2 and P2X7), or increasing spinal inhibition by enhancing monoaminergic activity, all offer exciting opportunities currently being validated in the clinic. Finally of note is the emergence of biological approaches, for example, antibodies, siRNA, gene therapy, offering powerful therapeutic additions with which to redress the neurological disease imbalances causing neuropathic pain.

Therapeutic potential of cannabis in pain medicine

Hosking, R. D., Zajicek, J. P. — 2008-06-13

Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic significance. Cannabinoids (CBs) are chemical compounds derived from cannabis. The major psychotropic CB delta-9-tetrahydrocannabinol (⁹-THC) was isolated in 1964 and the first CB receptor (CB₁R) was cloned in 1990. CB signalling occurs via G-protein-coupled receptors distributed throughout the body. Endocannabinoids are derivatives of arachidonic acid that function in diverse physiological systems. Neuronal CB₁Rs modulate synaptic transmission and mediate psychoactivity. Immune-cell CB₂ receptors (CB₂R) may down-regulate neuroinflammation and influence cyclooxygenase-dependent pathways. Animal models demonstrate that CBRs play a fundamental role in peripheral, spinal, and supraspinal nociception and that CBs are effective analgesics. Clinical trials of CBs in multiple sclerosis have suggested a benefit in neuropathic pain. However, human studies of CB-mediated analgesia have been limited by study size, heterogeneous patient populations, and subjective outcome measures. Furthermore, CBs have variable pharmacokinetics and can manifest psychotropism. They are currently licensed as antiemetics in chemotherapy and can be prescribed on a named-patient basis for neuropathic pain. Future selective peripheral CB₁R and CB₂R agonists will minimize central psychoactivity and may synergize opioid anti-nociception. This review discusses the basic science and clinical aspects of CB pharmacology with a focus on pain medicine.

Acute pain: combination treatments and how we measure their efficacy

McQuay, H. J., Poon, K. H., Derry, S., Moore, R. A. — 2008-06-13

Perioperative analgesic strategies are frequently tested using analgesic consumption as an outcome measure. This outcome measure is intuitive and superficially attractive, but has not been evaluated rigorously. Flaws in its use may be one explanation of continuing controversies surrounding the efficacy of analgesic strategies tested by this method. We contend that the analgesic consumption outcome measure is valid only when treatment groups achieve similar pain scores. A meta-analysis of perioperative gabapentin was used to test this hypothesis. Eighteen trials were identified, which were of sufficient methodological quality to include in the analysis. Trials reporting similar pain scores in treatment groups were classified as Category A and dissimilar scores as Category B. There were seven Category A trials: four reported reduced analgesic consumption with gabapentin compared with placebo, at one or more time points, and three found no difference. There were 11 Category B trials, all of which reported a decrease in analgesic consumption with gabapentin compared with placebo, at one or more time points. Analgesic consumption after gabapentin was similar for different postoperative analgesics. Sedation, dizziness, and vomiting were significant problems in pooled analysis. Analysis according to similarity of pain scores did not clarify whether perioperative gabapentin is useful in perioperative care. More rigorous examination of analgesic consumption as an outcome measure is needed, to establish whether achieving similar pain scores is as important as this paper claims and to determine those features of the analgesic delivery system, adverse effects, and other factors which may interfere with analgesic consumption as an outcome measure.

Chronic post-surgical pain: 10 years on

Macrae, W. A. — 2008-06-13

In the past ten years there has been recognition that chronic post-surgical pain is a significant problem. This is a complex area of research and although the quality of studies has improved many difficulties remain. Several recent publications have examined risk factors. Severe acute postoperative pain emerges as a factor that we may be able to influence. There is a need for education of the medical profession and the general public, so that effective measures are introduced and unnecessary and inappropriate operations minimized.

Translational medicine: cancer pain mechanisms and management

Delaney, A., Fleetwood-Walker, S. M., Colvin, L. A., Fallon, M. — 2008-06-13

Cancer-induced bone pain (CIBP) is a major clinical problem with up to 85% of patients with bony metastases having pain, often associated with anxiety and depression, reduced performance status, and a poor quality of life. Malignant bone disease creates a chronic pain state through sensitization and synaptic plasticity within the spinal cord that amplifies nociceptive signals and their transmission to the brain. Fifty per cent of patients are expected to gain adequate analgesia from palliative radiotherapy within 4–6 weeks of treatment. Opioid analgesia does make a useful contribution to the management of CIBP, especially in terms of suppressing tonic background pain. However, CIBP remains a clinical challenge because the spontaneous and movement-related components are more difficult to treat with opioids and commonly used analgesic drugs, without unacceptable side-effects. Recently developed laboratory models of CIBP, which show congruency with the clinical syndrome, are contributing to an improved understanding of the neurobiology of CIBP. This chronic pain syndrome appears to be unique and distinct from other chronic pain states, such as inflammatory or neuropathic pain. This has clear implications for treatment and development of future therapies. A translational medicine approach, using a highly iterative process between the clinic and the laboratory, may allow improved understanding of the underlying mechanisms of CIBP to be rapidly translated into real clinical benefits in terms of improved pain management.

Nerve blocks in palliative care

Chambers, W. A. — 2008-06-13

Although between 85% and 90% of patients with advanced cancer can have their pain well controlled with the use of analgesic drugs and adjuvants, there are some patients who will benefit from an interventional procedure. This includes a variety of nerve blocks and also some neurosurgical procedures. Approximately 8–10% of patients may benefit from a peripheral nerve block and around 2% from a central neuraxial block. The most common indication is because opioid dose escalation is limited by signs of opioid toxicity but some patients will benefit from one component of their pain being relieved by a simple peripheral block. Most patients about to undergo these procedures are already taking high doses of opiods and obtaining valid consent may pose problems. The use of peripheral nerve blocks, epidural and intrathecal infusions, and plexus blocks is discussed.

Pain in children: recent advances and ongoing challenges

Walker, S. M. — 2008-06-13

Significant advances in the assessment and management of acute pain in children have been made, and are supported by an increase in the availability and accessibility of evidence-based data. However, methodological and practical issues in the design and performance of clinical paediatric trials limit the quantity, and may influence the quality, of current data, which lags behind that available for adult practice. Collaborations within research networks, which incorporate both preclinical and clinical studies, may increase the feasibility and specificity of future trials. In early life, the developing nervous system responds differently to pain, analgesia, and injury, resulting in effects not seen in later life and which may have long-term consequences. Translational laboratory studies further our understanding of developmental changes in nociceptor pathway structure and function, analgesic pharmacodynamics, and the impact of different forms of injury. Chronic pain in children has a negative impact on quality of life, resulting in social and emotional consequences for both the child and the family. Despite age-related differences in many chronic pain conditions, such as neuropathic pain, management in children is often empirically based on data from studies in adults. There is a major need for further clinical research, training of health-care providers, and increased resources, to improve management and outcomes for children with chronic pain.

Advances in understanding the mechanisms and management of persistent pain in older adults

Karp, J. F., Shega, J. W., Morone, N. E., Weiner, D. K. — 2008-06-13

Older adults with persistent pain are not simply a chronologically older version of younger pain patients. Pain-related disability in older adults may be driven by pain ‘homeostenosis’, that is, diminished ability to effectively respond to the stress of persistent pain. Some of the comorbidities of ageing that can contribute to pain homeostenosis include cognitive and physical impairments, increased sensitivity to suprathreshold pain stimuli, medical and psychological comorbidities, altered pharmacokinetics and pharmacodynamics, and social isolation. A key distinction between older and younger individuals with persistent pain is the normal and pathological ageing-associated brain changes. These may alter the expression and experience of pain with impaired descending inhibition and dysfunction of pain gating mechanisms. Cognizance of these brain changes is needed to guide appropriate evaluation and treatment approaches. This paper reviews data that support these ageing-associated phenomena. Specifically, we discuss age-related changes in the brain (both normal and pathological) and in pain physiology; changes in experience and expression of pain that occur with dementia and contribute to pain homeostenosis; and unique aspects of age and pain-associated psychological function and their contribution to disability. We also present data demonstrating changes in brain morphology and neuropsychological performance that accompany persistent non-malignant pain in older adults and the treatment implications of these brain changes. Finally, preliminary data are presented on the efficacy of mindfulness meditation, a treatment that has been examined explicitly in older adults and targets optimizing brain function and descending inhibition.

Analgesia from a veterinary perspective

Flecknell, P. — 2008-06-13

The last decade has seen continued progress in both the recognition and management of animal pain. This upsurge in the use of analgesics in animals is welcome, but the main areas of use continue to be the control of postoperative or post-trauma pain, and the management of musculoskeletal pain, in companion animals and horses. The management of pain associated with other conditions, such as soft-tissue inflammation or cancer, is still relatively neglected. Pain management in farm animals, and in animals used in biomedical research could also be improved further. Apart from providing some interesting parallels with pain management in people, development of veterinary pain management has potentially much greater significance. For many years, animal pain management has benefited from the use of analgesics used in man. In the future, it may be that a better understanding of animal pain, and in particular chronic pain states, may lead to translation of therapies in the opposite direction.

Dobutamine and terlipressin in patients with septic shock

Miller, A., Coleman, N., Morelli, A., Ertmer, C., Westphal, M. — 2008-06-13

The modified ventilating tube changer to facilitate tracheal intubation using the GlideScope(R) in patients with a limited mouth opening

Xue, F. S., Yang, Q. Y., He, N., Xu, Y. C. — 2008-06-13

Acute withdrawal syndrome in a butorphanol-treated patient: an adverse combination of opioids

Igarashi, A., Amagasa, S., Yokoo, N., Sato, M. — 2008-06-13

Snakebite in pregnancy: preliminary study

Sarkar, S., Bhattacharya, P., Paswan, A. — 2008-06-13

Positioning the tracheal tube during percutaneous tracheostomy: another use for videolaryngoscopy

Gillies, M., Smith, J., Langrish, C. — 2008-06-13

Drug-eluting stent thrombosis in patients undergoing non-cardiac surgery

Ramakrishna, H., Godet, G., Le Manach, Y., Lesache, F., Perbet, S., Coriat, P. — 2008-06-13

Hatch & Sumner's Textbook of Paediatric Anaesthesia

Barker, I. — 2008-06-13

Careers in Anesthesiology: Autobiographical and Posthumous Memoirs

Wildsmith, J. A. W. — 2008-06-13

Cancer-related Bone Pain

Erdmann, A. — 2008-06-13

Emergencies in Clinical Medicine

Martin, F. — 2008-06-13