Pain is a perceived threat or damage to one's biological integrity. Suffering is the perception of serious threat or damage to the self, and it emerges when a discrepancy develops between what one expected of one's self and what one does or is. Some patients who experience sustained unrelieved pain suffer because pain changes who they are. At a physiological level, chronic pain promotes an extended and destructive stress response characterised by neuroendocrine dysregulation, fatigue, dysphoria, myalgia, and impaired mental and physical performance. This constellation of discomforts and functional limitations can foster negative thinking and create a vicious cycle of stress and disability. The idea that one's pain is uncontrollable in itself leads to stress. Patients suffer when this cycle renders them incapable of sustaining productive work, a normal family life, and supportive social interactions. Although patients suffer for many reasons, the physician can contribute substantially to the prevention or relief of suffering by controlling pain. Suffering is a nebulous concept for most physicians, and its relation to pain is unclear. This review offers a medically useful concept of suffering that distinguishes it from pain, accounts for the contributory relation of pain to suffering by describing pain as a stressor, and explores the implications of these ideas for the care of patients.

Opioids are our most powerful analgesics, but politics, prejudice, and our continuing ignorance still impede optimum prescribing. Just over 100 years ago, opium poppies were still grown on the Cambridgeshire fens in the UK to provide oblivion for the working man and his family, but the brewing lobby argued on thin evidence that their potions were less dangerous. The restriction of opioid availability to protect society and the individual continues in many countries. In this review I focus on chronic and cancer pain, but many of the principles apply in acute pain. The justification for this focus is that patients with chronic pain may suffer longer and unnecessarily if we prescribe and legislate badly.

Visceral pain is the most common form of pain produced by disease and one of the most frequent reasons why patients seek medical attention. Yet much of what we know about the mechanisms of pain derives from experimental studies of somatic not visceral nociception. The conventional view is that visceral pain is simply a variant of somatic pain, a view based on the belief that a single neurological mechanism is responsible for all pain. However, the more we learn about the mechanisms of somatic and visceral pain, the more we realise that although these two processes have much in common, they also have important differences. Although visceral pain is an important part of the normal sensory repertoire of all human beings and a prominent symptom of many clinical conditions, not much clinical research has been done in this field and there are few clinical scientists with expertise in the management of visceral pain. Instead, visceral pain is usually treated by a range of specialists who take quite different approaches to the management of this type of pain. Thus, the management of visceral pain is frequently unsatisfactory. In this review, we consider visceral pain as a separate form of pain and examine its distinct sensory properties from a clinical perspective. We describe recent research findings that may change the way we think about visceral pain and, more importantly, may help develop new procedures for its management.

Postanaesthesia care units used to echo with cries of patients in pain after general anaesthesia. Each as-needed dose of analgesia was given only after permission of the surgeon or anaesthesiologist. Once conscious, patients were required to request each subsequent analgesic dose until hospital discharge. Not surprisingly, nearly half the patients who have an operation experience moderate to severe pain after surgery. Acute pain control has advanced dramatically and is now a field with dedicated texts, journals, and research. Despite improved surgical techniques that have transformed many operations into same-day procedures, inadequately controlled pain may still extend the length of hospital stay and predispose to expensive, time-consuming complications such as pneumonia. Recognition of economic and humanitarian benefits of pain control has prompted worldwide attention from professional groups, insurers, and governments. This paper describes the process of acute pain and measures to control it with drugs or non-pharmacological interventions. Even brief intervals of acute pain can induce long-term neuronal remodelling and sensitisation ("plasticity"), chronic pain, and lasting psychologial distress. Hence, acute pain and other types of pain (cancer-related or chronic) that are classified as distinct actually have many similarities.

To assess the effects of zidovudine, didanosine, and zalcitabine on HIV disease progression and survival, we undertook meta-analyses of individual patient data and tabular data from all randomised trials that compared these agents.

We highlight current theories about peripheral neuropathic pain and show that progress in management is contingent on targeting treatment not at the aetiological factors or the symptoms but at the mechanisms that operate to produce the symptoms. This approach will require substantial progress in our understanding of the pathophysiology of neuropathic pain, the development of accurate diagnostic tools to discover what mechanisms contribute to the pain syndrome in an individual, and effective treatments aimed specifically at the mechanisms.

Human T-cell lymphotropic virus type I (HTLV-I) is the first human retrovirus to be associated with malignant disease--namely, adult T-cell leukaemia/lymphoma. HTLV-I has also been associated with several non-malignant conditions, notably the chronic neurodegenerative disorder, HTLV-I associated myelopathy (also known as tropical spastic paraparesis), infective dermatitis of children and uveitis. More recent evidence points to disease associations not previously linked to HTLV-I. Thus, the disease spectrum of HTLV-I is not fully known. HTLV-I has a worldwide distribution with major endemic foci in the Caribbean and southern Japan. The public health importance is confirmed by the major routes of transmission, which are mother-to-child, blood transfusion, and sexual activity. Unfortunately, no vaccine is available yet and there is no proven treatment for advanced HTLV-I disease.

Chronic pain is a common condition for which patients seek care from various health-care providers. This type of pain causes much suffering and disability and is frequently mistreated or undertreated. Patients who present for evaluation for chronic pain should undergo a careful assessment before therapy. Patients with chronic pain commonly experience depression, sleep disturbance, fatigue, and decreased overall physical and mental functioning. They frequently require an interdisciplinary model of care to allow care givers to address the multiple components of the patient's pain experience. After a careful evaluation, therapy may include medication, nerve blocks, active physical therapy, behavioural interventions, and assistance with vocational evaluation and training. Less frequently therapy may include placement of implantable devices to alter the pain experience. These patients suffer from a chronic condition and often require long-term care, with frequent reassessment and adjustment of therapy. Although cure is possible, it is also infrequent. Therefore, therapy is provided with the aim of decreasing pain and suffering while improving physical and mental functioning.

Low birthweight is associated with insulin resistance, hypertension, coronary-artery disease, and non-insulin-dependent diabetes (NIDDM). A suggested explanation for this association is intrauterine programming in response to maternal malnutrition. We propose, however, that genetically determined insulin resistance results in impaired insulin-mediated growth in the fetus as well as insulin resistance in adult life. Low birthweight, measures of insulin resistance in life, and ultimately glucose intolerance, diabetes, and hypertension could all be phenotypes of the same insulin-resistant genotype. There is evidence to support this hypothesis. Insulin secreted by the fetal pancreas in response to maternal glucose concentrations is a key growth factor. Monogenic diseases that impair sensing of glucose, lower insulin secretion, or increase insulin resistance are associated with impaired fetal growth. Polygenic influences resulting in insulin resistance in the normal population are therefore likely to result in lower birthweight. Abnormal vascular development during fetal life and early childhood, as a result of genetic insulin resistance, could also explain the increased risk of hypertension and vascular disease. The predisposition to NIDDM and vascular disease is likely to be the result of both genetic and fetal environmental factors.

A common assumption about pain is that it always results from the presence of underlying organic pathology. In the absence of objective pathology, an individual's report of pain may be ascribed to psychological causes. There is a wide variation in patient's experience of pain and organic factors alone cannot explain individual differences in patients' reports. Assessment of patients who report pain requires attention to psychosocial, behavioural, and organic factors. We describe a comprehensive approach to the assessment of psychological and behavioural variables that affect patients' reports of pain. We counter the duality of the somatogenic versus psychogenic perspective and suggest a more integrated assessment that encompasses not only the severity of pain and related physical pathology but also the person who is reporting the presence of pain.

Lichen sclerosis is a chronic inflammatory skin disease that causes substantial discomfort and morbidity, most commonly in adult women, but also in men and children. Any skin site may be affected (and, rarely, the oral mucosa) but lichen sclerosus is most common in the anogenital area, where it causes intractable itching and soreness. In children, the disorder may be confused with changes seen in sexual abuse. Progression to destructive scarring is common. There is increased risk of developing vulval cancer, and there are links with penile cancer. Patients should be kept under long-term review. Lichen sclerosus can occur without symptoms, and the exact prevalence is uncertain. It occurs most commonly in women at times of low sex hormone output. The underlying cause is unknown, but there seems to be a genetic susceptibility and a link with autoimmune mechanisms. The wart virus and the spirochaete borrelia have been suggested but not substantiated as infective triggers. The Koebner phenomenon is known to occur (lichen sclerosus occurs in skin already scarred or damaged), so trauma, injury, and sexual abuse have been suggested as possible triggers of symptoms in genetically predisposed people. The treatment of choice for anogenital lichen sclerosus is potent topical corticosteroid ointment for a limited time. Circumcision may be indicated in men, and surgery may be considered in women, to relieve effects of scarring or to treat coexisting carcinoma. Current research aims to identify a treatable cause of lichen sclerosus, to identify patients at risk of scarring and of malignant disorders, and to find target pathways for therapeutic intervention.

Understanding the plasticity of pain and analgesia exhibited in different pain states may improve therapies for the two major types of pain, neuropathic and inflammatory pain, in which nerve and tissue damage leads to alterations at both peripheral and central levels. At the level of the peripheral nerve, drugs that act on particular sodium channels may target only pain-related activity. Agents that act on some of the peripheral mediators of pain may control peripheral nerve activity. A new generation of non-steroidal anti-inflammatory drugs, cyclo-oxygenase 2 inhibitors, that lack gastric actions are becoming available. In the spinal cord, the release of peptides and glutamate causes activation of multiple receptors, particularly, the N-methyl-D-aspartate receptor for glutamate, which, in concert with other spinal systems, generates spinal hypersensitivity. Blocking the generation of excitability is one approach, but increasing inhibitions may also provide analgesia. Opioid actions are via presynaptic and post-synaptic inhibitory effects on central and peripheral C fibre terminals, spinal neurones, and supraspinal mechanisms. Our knowledge of brain mechanisms of pain is still, however, limited. Other new targets have been revealed by molecular biology and animal models of clinical pain, but the possibility of a "magic bullet" is doubtful. Thus, another approach could be single molecules with dual drug actions, that encompass targets where additive or synergistic effects of different mechanisms may enable pain relief without major adverse effects.

Until the 1960s, pain was considered an inevitable sensory response to tissue damage. There was little room for the affective dimension of this ubiquitous experience, and none whatsoever for the effects of genetic differences, past experience, anxiety, or expectation. In recent years, great advances have been made in our understanding of the mechanisms that underlie pain and in the treatment of people who complain of pain. The roles of factors outside the patient's body have also been clarified. Pain is probably the most common symptomatic reason to seek medical consultation. All of us have headaches, burns, cuts, and other pains at some time during childhood and adult life. Individuals who undergo surgery are almost certain to have postoperative pain. Ageing is also associated with an increased likelihood of chronic pain. Health-care expenditures for chronic pain are enormous, rivalled only by the costs of wage replacement and welfare programmes for those who do not work because of pain. Despite improved knowledge of underlying mechanisms and better treatments, many people who have chronic pain receive inadequate care.

The development of coronary artery bypass grafting (CABG) and its effect on angina is the product of a series of technical and scientific advances. Despite these advances, however, adverse neurobehavioural outcomes continue to occur. Stroke is the most serious complication of CABG, but studies that have identified demographic and medical risk factors available before surgery are an important advance. Short-term cognitive deficits are common after CABG, but may not be specific to this procedure. However, deficits in some cognitive areas such as visuoconstruction persist over time, and may reflect parieto-occipital watershed area injury secondary to hypoperfusion or embolic factors. Risk factors for cognitive decline may be time dependent, with short-term studies identifying factors that differ from those of long-term studies. Patients with depression before surgery are likely to have persistent depression afterwards. However, depression does not account for the cognitive decline after CABG. Since CABG is increasingly done in older patients with more comorbidity, the challenge is to identify patients at risk of adverse neurocognitive outcomes and to protect them by modification of the surgical procedure or by effective medical therapy.