Malignant bone pain: Pathophysiology and treatments

Metastatic involvement of the bone is one of the most frequent causes of pain in cancer patients and represents one of the first signs of widespread neoplastic disease. The pain may originate directly from the bone, from nerve root compression, or from muscle spasms in the area of the lesions. The mechanism of metastatic bone pain is mainly somatic (nociceptive), even though, in some cases, neuropathic and visceral stimulations may overlap. The conventional symptomatic treatment of metastatic bone pain requires the use of multidisciplinary therapies, such as radiotherapy, in association with systemic treatment (hormonotherapy, chemotherapy, radioisotopes) with the support of analgesic therapy. Recently, studies have indicated the use of bisphosphonates in the treatment of pain and in the prevention of skeletal complications in patients with metastatic bone disease. In some patients, pharmacologic treatment, radiotherapy, and radioisotopes administered alone or in association are not able to manage pain adequately. The role of neuroinvasive techniques in treating metastatic bone pain is debated. The clinical conditions of the patient, his life expectancy, and quality of life must guide the physician in the choice of the best possible therapy.     

Malignant hyperthermia: pathophysiology, clinical presentation, and treatment

Malignant hyperthermia (MH) was first described as an inherited highly lethal disorder in 1960. There has since been significant progress in the clinical management, identification of MH susceptible (MHS) persons, and understanding of the underlying pathophysiology. When patients are known to be MHS prior to surgery, an MH episode can easily be avoided by the use of safe nontriggering anesthetic agents. Current MH mortality is <10%, but many experts believe this can be significantly reduced by improved MH preparedness. MH is triggered in humans by an MH triggering anesthetic agent, which causes the release of calcium from the sarcoplastic reticulum of the skeletal muscle cell at an uncontrolled rate resulting in a hypermetabolic state. Recent molecular genetic studies have shown that MH is related to an abnormal ryanodine receptor that controls the release of calcium from the sarcoplastic reticulum. This article reviews the current understanding of the pathophysiology, diagnosis, clinical presentation, and treatment of MH.     

The pathophysiology of cancer-induced bone pain: current understanding

Cancer-induced bone pain (CIBP) is a common clinical problem. Although treatment has been revolutionised in the past 10 years with the introduction of bisphosphonates, pain arising spontaneously or from movement, remains a leading cause of unresolved pain in many patients. Until recently little was understood about the peripheral and central mechanisms of bone pain. Insight into the mechanisms of osteoblast and osteoclast activation, via receptor activator for nuclear factor KB (RANK) dependent and independent mechanisms and a re-evaluation of primary afferent terminals within bone have led to a suggestion that CIBP may be a mixture of inflammatory and neuropathic stimuli. The recently published animal model of localised but progressive bone destruction has allowed greater insight into the peripheral and dorsal horn pathophysiology, which hitherto was precluded. Immunocytochemical markers of neurotransmitters and receptors indicate that CIBP has unique characteristics, unlike neuropathy or inflammation. Evidence for an increased excitability within the dorsal horn, and especially Lamina I, and possible mechanisms underlying this unique pain state will be discussed.     

Metastatic bone cancer pain: Etiology and treatment options

Painful metastatic bone disease remains a challenge for physicians. The treatment choices available are wide and varied, with each having its appropriate place in the management of painful bone metastases. Radiotherapy remains the mainstay of treatment with or without surgery. Advances in understanding the intricate pathway responsible for pain generation and the addition of agents such as bisphosphonates to the physician’s armamentarium further assist in the management of painful bone metastases.     

Gas embolism: pathophysiology and treatment

Based on a literature search, an overview is presented of the pathophysiology of venous and arterial gas embolism in the experimental and clinical environment, as well as the relevance and aims of diagnostics and treatment of gas embolism. The review starts with a few historical observations and then addresses venous air embolism by discussing pulmonary vascular filtration, entrapment, and the clinical occurrence of venous air emboli. The section on arterial gas embolism deals with the main mechanisms involved, coronary and cerebral air embolism (CAE), and the effects of bubbles on the blood-brain barrier. The diagnosis of CAE uses various techniques including ultrasound, perioperative monitoring, computed tomography, brain magnetic resonance imaging and other modalities. The section on therapy starts by addressing the primary treatment goals and the roles of adequate oxygenation and ventilation. Then the rationale for hyperbaric oxygen as a therapy for CAE based on its physiological mode of action is discussed, as well as some aspects of adjuvant drug therapy. A few animal studies are presented, which emphasize the importance of the timing of therapy, and the outcome of patients with air embolism (including clinical patients, divers and submariners) is described.     

Physiology and pathophysiology of visceral pain

Visceral pain is diffusely localized, referred to deep somatic tissues, skin and viscera, frequently not correlated with an actual trauma, commonly correlated with strong negative affective reactions and accompanied by strong protective autonomic and motor reactions. It is correlated with the excitation of spinal (thoraco-lumbar, sacral) visceral afferents and (with a few exceptions) not with the excitation of vagal afferents.Spinal visceral afferents are polymodal and can be excited by physical and chemical stimuli. All groups of visceral afferents can be sensitized (e.g.by inflammation). Normally silent (mechanically insensitive) visceral afferents are recruited by inflammation. Individual visceral afferent neurons project in laminae I and V of the dorsal horn over several segments, medio-lateral over the entire width of the dorsal horn and to the contralateral side. Their activity is synaptically transmitted, in these and deeper laminae, to viscero-somatic convergent neurons which receive additional afferent synaptic input from skin and deep somatic tissues of the corresponding dermatomes,myotomes and sclerotomes. The mechanism of sensitization of viscerosomatic convergent neurons (central sensitization) during sensitization of spinal visceral afferents is unclear.Viscero-somatic tract neurons project to lower and upper brain stem,hypothalamus and via the thalamus to various cortex areas.Visceral nociception and pain is presumably (together with other visceral sensations and homeostatic regulations of autonomic body functions) primarily represented in the insula in the context of interoception. The insula obtains its main peripheral afferent input from lamina I neurons via the Nucleus ventromedialis posterior of the thalamus.The transmission of visceral impulses in the spinal cord is modulated by the endogenous control systems in the brain stem which are in turn under the control of cortex and limbic system.     

Nephrotic syndrome: pathophysiology and treatment

Nephrotic syndrome refers to the symptoms caused by renal injury in which large amounts of protein are lost in the urine. Common manifestations of the syndrome are proteinuria, edema, hypoalbuminemia, hyperlipidemia, and hypercoagulability. Recent research has presented findings that contradict some of the accepted theories regarding the pathophysiology of some symptoms of the syndrome. Accurate understanding of these pathophysiological mechanisms underlying the symptoms seen in nephrotic syndrome is necessary for caregivers to determine the appropriate treatment for these patients.     

骨转移癌及其骨痛的综合治疗进展

疼痛是癌症患者最常见的症状之一,严重影响癌症患者的生活质量,目前临床研究已经证明综合治疗不但能有效地缓解患者的疼痛症状,全面改善患者的生活质量,而且能减轻肿瘤的负荷,延长其生存时间。因此本文章拟对综合治疗在疼痛性骨转移瘤的作用方面作一简要的综述。     

The pathophysiology of pain.

Recent advances in elucidating the physiologic transmission of pain have lead to new targets for analgesic drug development. New agents are being studied in animal trials and familiar drugs are being investigated in novel ways. This paper was written to familiarize nurse anesthetists with one of the new targets, ionotropic glutamate receptors. This article begins with a brief survey of several alternate theories of the origin of pain, then, in more detail, describes the anatomical and physiological basis of pain, focusing on the phenomenon of central sensitization and the role of ionotropic glutamate receptors. An exploration of several recent pharmacological studies targeting N-methyl-D-aspartate receptors concludes the review.     

The pathophysiology of acute pain

The method by which the body detects, interprets, and responds to painful stimulation is tantamount to an orchestral concert, with each individual instrument contributing a subtle yet important element composing the finished product. The polymodal peripheral receptors initiate unpleasant sensations that can be modulated in the dorsal horn and the anterior columns of the spinal cord before reaching the cerebral cortex. Despite similar neurological "wiring," pain sensations from the skin are not the same in character as those from visceral organs. A reaction of pain is based upon interpretation in specific cerebral centers and the resultant motor function. With the advent of functional MRI and PET scanners, the understanding of the cerebral interpretation of pain is expanding. Remember as well that emotional and psychological factors are crucial in pain perception, and are the starting points for any individual's perception of a painful circumstance.     

The anatomy and pathophysiology of neck pain

Neck pain should not, and must not, be confused with cervical radicular pain. Equating the two conditions, or confusing them, results in misdiagnosis, inappropriate investigations, and inappropriate treatment that is destined to fail. So critical is the difference that pedagogically it is unwise to include the two topics in the same book, let alone the same article. However, traditions and expectations are hard to break. In deference to habit, this article addresses both entities, but does so by underplaying cervical radicular pain so as to retain the emphasis on neck pain.     

Necrotizing fasciitis: pathophysiology and treatment.

Necrotizing fasciitis (NF) is a life-threatening bacterial infection causing necrosis of the fascia, underlying skin, and vasculature. NF spreads rapidly, making immediate diagnosis important for survival. Treatment may involve the administration of several broad-spectrum antibiotics, surgical debridement, and skin grafting. In the following two articles, the pathophysiology, medical management, and nursing care of patients are discussed. An in-depth model care plan illustrates the complexity of the disease and its treatment.     

The anatomy and pathophysiology of neck pain

This article carefully itemizes the various anatomic structures that can evoke neck pain, putting in perspective what clinicians know, what they assume, and what they need to understand better about neck pain and pain referred from the neck. The critique of many of the accepted entities in the differential diagnosis of neck pain is crucial to an understanding of the causes of neck pain and an ability to implement appropriate therapies.     

Symptomatology and clinical pathophysiology of myofascial pain

Myofascial pain syndromes, fibromyalgia, and articular dysfunctions may all be contributing to our patients' ubiquitous musculoskeletal pain problems that generally are poorly understood and poorly managed. Thepectoralis minor myofascial pain syndrome, for example, results from trigger points (TrPs) activated by stress overload of the muscle. Symptoms of pain referred to the shoulder and ulnar aspect of the arm and forearm, and of pain on reaching around and behind the body, are characteristic. Findings include restricted stretch range of motion and some weakness of the muscle, taut bands of muscle fibers, and focal trigger point tenderness of each taut band on palpation. Snapping palpation at the TrP elicits a local twitch response (LTR). The increased muscle tension of a pectoralis minor syndrome commonly entraps the lower trunk of the brachial plexus, producing symptoms of a cervical radiculopathy.     

Renal artery stenosis: pathophysiology and treatment

Renal artery stenosis (RAS) is a disease that consists of a broad spectrum of different entities with different pathophysiologies that require varied approaches to diagnosis and treatment. The two most common causes of RAS are fibromuscular dysplasia and atherosclerosis, which consist of approximately 10 and 90% of RAS, respectively. Renovascular diseases are divided into two broad subtypes: hypertension and nephropathy. While models explaining the pathophysiology of RAS indicate a direct relationship between RAS and renovascular hypertension and nephropathy, this has not been fully seen in humans with chronic arterial narrowing. Furthermore, clinical data from humans has not fully demonstrated the benefit one would expect from treatment of RAS with regards to improvement in renovascular hypertension and nephropathy. The goal of this article is to review the pathophysiology of RAS, and discuss outcomes of treatment with regard to renovascular hypertension and nephropathy.