Disease and Pain.
The Common vein Copyright 2008
James Armstrong PA Ashley Davidoff MD
inflammation |
infection |
neoplasm |
mechanical |
obstruction |
distension |
trauma |
ischemia |
hemorrhage |
dissection |
rupture |
Introduction
As shown in the section on classification of pain in the basic science series, and repeated in the diagram below, there are many disorders that cause pain.
Acute somatic pain signifies imminent and possibly dangerous bodily injury. Its presence evokes an immediate reaction either with a simple reflex or complex reaction. The pain comes and goes and the body as an organism proceeds in a normal fashion thereafter. The pain becomes an experience of the past and is memorialized as a learning experience in the brain. The result is a better prepared response to a similar insult in the future.
Disease however happens! It comes in the context of many pathologies and the body does not like it. Inflammation is commonly the underlying pathophysiology for many of the disorders. Disease is usually (but not exclusively) an intrusion of the visceral sensory system and although the discomfort is still classified as pain, the experience is very different from the acute somatic experience described above. The pain of disease begins as one experience, butmay often fluctuate in parallel to the dynamic reactions of the body as it attempts to counteract the natural history of the inciting process.
Traumatic injury, as in the case of a bone fracture, is easily understood in this vein. On an average of 4-6 weeks healing time, the pain gradually subsides. The inciting injury and bodily response are both finite and predictable. If on the other hand, a chronic progressive or slowly healing disease ensues, then the pain syndrome will reflect the net result of healing versus ongoing pathology.
As shown in the section on classification of pain in the basic science series, and repeated in the diagram below, there are many disorders that cause pain.
Acute somatic pain signifies imminent and possibly dangerous bodily injury. Its presence evokes an immediate reaction either with a simple reflex or complex reaction. The pain comes and goes and the body as an organism proceeds in a normal fashion thereafter. The pain becomes an experience of the past and is memorialized as a learning experience in the brain. The result is a better prepared response to a similar insult in the future.
Disease however happens! It comes in the context of many pathologies and the body does not like it. Inflammation is commonly the underlying pathophysiology for many of the disorders. Disease is usually (but not exclusively) an intrusion of the visceral sensory system and although the discomfort is still classified as pain, the experience is very different from the acute somatic experience described above. The pain of disease begins as one experience, butmay often fluctuate in parallel to the dynamic reactions of the body as it attempts to counteract the natural history of the inciting process.
Traumatic injury, as in the case of a bone fracture, is easily understood in this vein. On an average of 4-6 weeks healing time, the pain gradually subsides. The inciting injury and bodily response are both finite and predictable. If on the other hand, a chronic progressive or slowly healing disease ensues, then the pain syndrome will reflect the net result of healing versus ongoing pathology.
Classification of Pain |
However, when disease directly impairs the nervous system, the pain becomes neuropathic and not necessarily related to either the aggressiveness of the disease or healing. This is more complex and harder to treat. Such pain occurs with chronic inflammation, chronic ischemia and malignant disease for example. This pain is less dependent on healing rates but more so on the premise of whether or not healing occurs at all. Neuropathic pain can become debilitating and sometimes unrelenting.The complexity that may be added by ongoing social, cultural, and psychological responses makes this the most difficult pain to comprehend on a physical level. We will discuss neuropathic pain in the organic disease section which follows.
The mechanisms through which patients experience pain differ according to the injurious process and tissue response. Below we describe the classical disease processes, each with a unique mechanism and subsequent pain signal. The diseases that involve the somatic receptors tend to present with acute pain. Examples including skin lacerations, meningitis, pericarditis, pleurisy, peritonitonitis, and periostitis cause sharp pain. As you may have noted the suffix, “itis” in may of these conditions, tells us that these are all of an inflammatory nature.
41819c02 Courtesy Ashley Davidoff MD medical students code chest CXR imaging lung plain film pneumonia radiology resolution |
42540c02a01 lung consolidation pleuritic pain pneumonia RUL pneumonic infiltrate pain on inspiration pleura paietal pleura cough Davidoff Art Courtesy Ashley Davidoff MD |
Diseases that incite the visceral nociceptors commonly evolve from an increase in pressure within an organ. Distension forces may cause physiological cramps due to “gas pain”, menstrual cramps, and labor. More serious cramps may be caused by obstructive disease processes like bowel obstruction, renal colic, and bilary colic. Many diseases like acute cholecystitis, appendicitis, and cholangitis are a combination of the two.
16157c01s.81 gallbladder edematous wall distended gall bladder edema in the wall fluid in the fat surrounding the gallbladder indurated fat free fluid in Morrison’s pouch acute cholecystitis stones not visible on CT scan pain peritonitis Murphy’s sign inflammation CTscan Courtesy Ashley Davidoff Copyright 2008 All rights reserved |
The primary response to any injury in the human body is inflammation. This is an immune mediated defensive cascade of events, initiated by increased vascular perfusion and permeability to the area of insult. Next, a fusion of cellular migration and degranulation leads to a release of peptides that stimulate, among other things, specialized cellular pain receptors known as proteinases. The subsequent signals generated by inflammation cause symptoms that include burning, aching and pressure.
Sensitization of Receptors With Tissue Injury – Changing Thresholds
Within the extracellular space, there are many substances that affect the sensitivity of the free nerve endings, usually to increase the sensitivity or lower the threshold to pain. Inflammation is a classic example as a phenomenon that characteristically induces the production of a variety of extracellular susbstances that either incite pain or sensitize the nerve endings to pain.
prostaglandin serotonin bradykinin potassium substance P mast cell histamine vasodilation nociceptors pain receptors Davidoff art Copyright 2008 83169b11.8s |
Pain, or its Latin equivalent “dolor”, is one of the classical hallmarks of inflammation as was described in the latter half of the second century AD by Celsus, a Greek philosopher. Anti-inflammatory agents, mild heat, and cooling tend to reduce the inflammatory reaction and thus reduce the pain. They provide relief by neutralizing the effect of the substances that sensitize or incite the pain.
The pain sensitizing peptide compounds released as a consequence of tissue injury include prostaglandins, serotonin, bradykinin and potassium. They in turn stimulate a local axonal reflex causing the free nerve endings to release substance P or calcitonin and some gene related peptides (CRGP). Substance P and CGRP cause mast cells to release histamine which in turn causes vasodilation and local edema, other hallmarks of the inflammatory process. Some of these substances activate pain through the chemoreceptors including ATP prostanoids and hydrogen ions (acid PH).
This mechanism has one process in mind for you and that is to rest the injured part. A fractured arm becomes hypersensitive to touch or pressure and induces you to hold the part as still as possible, sometimes even employing your other hand and arm to hold the injury as still as possible. This forces one to pure rest to promote healing and to progress without further injury.
Infection most often manifests as inflammation. However the pattern and subsequent pain are different. Infection by nature, delays healing. Pain complaints will therefore be more prolonged and progressive. Subsequently, inflammatory pain from infection will endure, deepen or spread until treatment and healing is initiated.
78031c04.8s pain back thoracic spine intervertebral disc discitis diskitis osteomyelitis soft tissue changes paravertebral periostitis periosteum bone destruction tuberculosis TB question CTscan Courtesy Ashley DAvidoff MD copyright 2008 |
Pain in the setting of neoplasm may be acute or chronic and variably related to the cancer. Somatic pain is most commonly related to metastatic bony involvement irritating the periosteum. There may be tumor induced osteolysis with release of prostaglandin E2 which sensitizes the nerves. When the metastases are in the vertebral column, compression fractures or expansile mechanical changes may impinge on the nerves or spinal cord and induce neuropathic pain. Bone involvement may become manifest as a somatic throbbing or aching pain.
75598.8cs03 bone lumbar spine metastasis compression fracture lytic metastases CT scan Courtesy Ashley Davidoff MD copyright 2008
|
When cancer pain is visceral in origin, it is due to pressure effects as the tumor occupies space. In this instance, mechanical nociceptors are stimulated. Alternatively, tissue damage may release of a variety of chemicals including cytokines. K+, bradykinin, interleukin and growth factors that stimulate chemical nociceptors and promote inflammation and a decreased pain threshold. Impingement on nerves or the spinal cord may cause neuropathic pain.
Cancer therapy may also cause pain due to tissue burns from radiation or localized pain at the sight of a chemotherapy injection. Pharmacotherapy, specifically the vinca alakaloids platinols or tamoxifen may also cause pain that may be neuropathic.
24008 liver fx mass portal vein fx invasion satellite nodule multicentric dx hepatocellular carcinoma hepatoma HCC grosspathology Courtesy Barbara Banner MD
|
83037c03.8s 70 F presents with right lower quadrant pain RLQ colon cecum mass colon carcinoma napkin ring peritoneum peritonism somatic pain induration CTscan Courtesy Ashley Davidoff MD copyright 2008 |
Pressure sensitive nociceptors are positioned in both the somatic regions but predominate in the viscera. Stimulation of the pressure sensitive nociceptors is perceived as aching or throbbing and is characteristic of a range of cramps and colic that are “normal” day to day sensations to the more severe pain of childbirth.
87559pb04b02b11.8s pressure receptors nociceptors mechonoreceptors free nerve endings trees in the body Davidoff art copyright 2008 |
These pains however are seen in pathological situations and the word “ache” or “cramps” seemingly and incorrectly implies a lack of severity. Anybody who has experienced renal colic will tell you that the pain is probaly the most severe pain they have experienced. In fact the stone that can induce the worst pain need only be 2-3mms in diameter or less.
Another pain pathway in the body arises from gamma sensors located in the muscle spindle apparatus of skeletal muscle. These receptors may be activated at rest or with motor function depending on the source. The most common form of muscular pain occurs after strenuous activity when muscle spindles have become relatively overused through stretching and contracting. The resultant achy pain associated with movement has often been controversially described as secondary to lactic acid and oxygen debt to the muscle fibers. One confounding factor however is that neuropathic pain is also transmitted in the same apparatus but at rest. Patients with spinal cord injuries may suffer from muscular pain as part of a syndrome called Central Pain.
Obstruction of any of the tubular systems within the body and particularly of the gastrointestinal tract can cause pain by stimulating mechanical and pressure sensitive nociceptors in the viscera. The afferent nerve fibers are situated within the viscera and are commonly carried by similar afferent fibers of the sympathetic system.
83149c02.8s right flank pain kidney renal pelvis ureter stone ureterolithiasis hydronephrosis pain delayed nephrogram CTscan Courtesy Ashley Davidoff MD copyright 2008 |
Less severe forms of visceral pain also occur in other obstructive diseases such as small bowel obstruction. There may be many causes but the most common is adhesions from prior surgery. The pain is often accompanied by nausea and vomiting.
00554 small bowel fx dilated fx enlarged dx SBO obstruction plainfilm Courtesy Ashley Davidoff MD DB |
The pain described above is caused by distension but there are other causes of distension that can induce pain. The sudden stretching of a capsule induced by edema, hematoma, or a subacute accumulation of pus can induce pain that can be somatic or visceral.
Trauma can cause pain in many ways including local and systemic manifestations. Somatic,visceral, neuropathic, inflammatory, infectious, mechanical, metabolic, and chemical influences all can play a role.
artery bone trauma fracture post op pain artery digital trauma angiography angiogram fractures Courtesy Ashley DAvidoff MD copyright 2008 17496c02.8s
|
Ischemic Pain and other Circulatory Disorders
Insufficient perfusion of tissue leads to hypoxia which is usually manifested as pain. The discomfort may be somatic as in the classic muscular ache of claudication, or visceral as described by waxing and waning abdominal pain of ischemic bowel syndrome. The pattern of provoking or relieving factors are helpful descriptors in characterizing the supply and demand mismatch of compromised blood flow.
The biochemical changes by nature are complex, but include the loss of high-energy compounds and acidosis due to anaerobic production of lactate. Hydrogen ions are potent stimulators of pain nociceptors. Other algesiogenic chemicals include substance P, K+, kinins, interleukins, adenosine, histamine, and leukotrines. Adenosine has strong associations with ischemic pain as well.
87559pb04b02b02b02.8s nociceptors chemical receptors free nerve endings trees in the body hydrogen ion algogenic substances autocids substance C K+ kinins interleukins adenosine histamine leukotrines H+ Davidoff art copyright 2008
|
Angina is a common and often debilitating manifestation of ischemic disease. In this case, there is deficiency of oxygen to cardiac muscle inducing discomfort with exercise that is relieved by rest. The underlying cause is narrowing of the coronary arteries by atherosclerosis.
Courtesy Ashley Davidoff MD. 07023c code heart artery coronary circumflex stenosis atherosclerosis imaging radiology angiography overlay |
Other Vascular and Circulatory Disorders
Migraine
The blood vessel wall is richly endowed with nociceptors and the pain of migrainous headaches are thought to have a vascular origin. The newer neurovascular theory suggests that the inciting event is a cortical disorder that subsequently causes the vessels to vasodilate and constrict. It is these events which are responsible for the pain.
Venous Congestion
Venous congestion can cause pain on many levels. It is classically seen in patients with acute inflammation. Due to a combination of higher pressures, chemical forces and the vascular response, edema ensues, causing and contributing to the pain. In other patients, the venous congestion may cause swelling of the involved organ and an increase in visceral pressure thus stimulating nociceptors. In patients with acute tricuspid regurgitation, swelling of the liver causes distension of the liver capsule and a somatic type pain. Pelvic congestion syndromes seem to arise from pelvic varicocities commonly acquired during pregnancy and the source of a constant dull pelvic ache. A tiredness or discomfort of the legs is a similar symptom that patients with varicose veins complain of.
Hemorrhage can cause a variety of pain syndromes ranging from no pain at all such as occurs in a GI bleed, to a mild visceral ache from a muscle bruise, to incapacitating headache pain caused by rupture of a berry aneurysm in the brain.
89081pd04b02.8s pain headache sleep woken awakened from sleep worst pain in my life headache 10 out of 10 ruptured berry aneurysm bleed blood hemorrhage meninges somatic Davidoff art copyright 2008 |
76059c01 52 male headache neurological deficit normal abnormal brain cerebrum subarachnoid blood subarachnoid hemorrhage Sylvian fissures midbrain basal cisterns cerebellar folia circle of Willis cerebellum sulcus sulci ambient cisterns 4th ventricle dx probable rupture of basilar tip aneurysm berry aneurysm CTscan Courtesy Ashley Davidoff MD 76059c01 76059c02 76059c03 |
The patient who presents with acute severe back pain, hypotension, and a pulsatile abdominal mass has a diagnosis of a ruptured abdominal aortic aneurysm until proven otherwise. Action should include a prompt and urgent phone call to the vascular surgeon, a phone call to the OR, and an immediate non contrast CT of the abdomen and pelvis. The pain is mostly caused in this instance by a sudden distension of the retroperitoneal tissues inciting deep muscle and connective tissue mechanoreceptors and presumably causing tissue damage with the release of chemicals that incite the chemoreceptors.
An acute aortic dissection is a cause of hyperacute back pain caused by rapid accumulation of blood within the aortic wall. The subsequent distension incites the pressure receptors. In addition, there may be dissection across the intercostal arteries which become occluded. The pain is often somatic and lancinating due to resultant ischemia of the chest wall. When the dissection involves the ascending aorta, the pain is usually in the anterior chest. A dissection extending to the descending aorta may cause interscapular pain. Aortic dissections can also involve and occlude the right coronary artery in which case it may cause classical cardiac ischemic pain.
Courtesy Henri Cuenoud MD 13421 code CVS thorax AO aorta dissection grosspathology |
20448c03.8s descending aorta ascending aorta fx dissection fx crescent dx aortic dissection type A CTscan Courtesy Ashley Davidoff MD DB |
Other Hemorrhages and Ruptures
Pulmonary hemorrhage can be extensive but painless as the pulmonary parenchyma is not nociceptive. However the pleura are richly endowed with nociceptors and when pleura is involved with inflammation as noted above, pain can be sharp and somatic.
47711c01 20 year old male presents with hemoptysis and renal failure chest lungs upper lobes lower lobes infiltrates acinar infiltrates fluffy infiltrates almost symmetrical fx bilateral pulmonary infiltrates renal biopsy dx Wegener’s granulomatosis with pulmonary hemorrhage blood character CTscan Daviddoff MD 47711c02 |
Hemorrhage into the peritoneal cavity is also surprisingly non-painful, though hemorrhage into the omentum as seen in trauma and following rupture of an ovarian hemorrhagic cyst can be extremely painful. The patient may present with peritonism and simulate peritonitis.
44692c.8s young college football player who presents with RUQ pain and fever with normal gallbadder by USscan fx mesentery greater omentum transverse colon large bowel RUQ fx induration dx hemorrhagic bleeding of right sided component of colonic greater omentum due to traumatic injury surgical proof CTscan coronal ddx appendagitis Courtesy Ashley Davidoff MD 44692 44694 gastrocolic ligament lesser omentum copyright 2008 |
Ectopic pregnancy is another clinical scenario where a combination of rupture and hemorrhage creates an extremely painful and dramatic clinical presentation.
75791c03 32 year old female presents with abdominal pain and pelvic pain positive HCG uterus endometrial stripe a = left ovary complex free fluid probably blood and hemorrhage b = left ovary complex free fluid probably blood and hemorrhage c = viable fetus in the left adnexa with fetal doppler flow heart beat d = crown rump length of .62cms corresponding to a gestational age of 6 weeks and 4 days dx left sided ectopic pregnancy US scan Courtesy Ashley Davidoff MD 75791 75791c01 75791c03 75792c01 |
The metabolic causes of abdominal pain tend to be quite uncommon. One example, diabetic ketoacidosis will cause pain from the acute fatty change of the liver with swelling and capsular distension. Abdominal pain in an Addisonian crisis is also described but the condition is rare. Porphyria, another rare metabolic disorder is a genetic defect resulting in a paucity of the enzyme porphobilinogen-deaminase. The deficiency causes an accumulation of precursors, porphobilinogen and amino-levulinic acid (ALA) which induce an autonomic neuropathy and hence pain.
Functional pain is common, complex and often a diagnosis of exclusion. This pain is usually a collection of many diseases that have psychosocial and psycho-cultural elements that are difficult to define and difficult to treat. Many headaches, tension aches, atypical chest pains, vague abdominal pains, irritable bowel syndrome, chronic functional abdominal pain, fibromyalgia, chronic fatigue syndromes fit into this category.
Pain is a common symptom and can reflect a wide variety of diseases. Inflammatory and mechanical injury are the most common causes of pain. The chemical mediators produced by these insults either lower the threshold to pain or induce pain themselves. Embryology and the distribution of pain receptors account for variations in pain perception. There are nociceptors sensitive to pricking or sharp objects that exist in high concentration in the somatic structures thus producing sharp, well localized pains. On the other hand, nociceptors sensitive to pressure are concentrated in the viscera and produce ill defined dull aches. Cross over situations occur and anybody experiencing gas cramps would agree that their pains are far from dull. In addition, there are many situations where somatic and visceral pains are both present as was described in the case of acute cholecytitis. Neuropathic pain is not as common as the somatic and visceral pain and tends to manifest as chronic pain. Functional pains are common, complex and difficult for both the patient and the caregiver. Often treatment of this pain type is multimodal and requires a combination of experts to direct management.
83209c.81s 40 year female pregnant pregnancy presents with acute abdominal pain MRI shows a sponataneous subcapsular hematoma hemorrhage liver subcapsular hematoma blood HELLP syndrome: “H” for hemolysis (breakage of red blood cells), “EL” for elevated liver enzymes, “LP” for low platelet count complication of preeclampsia and eclampsia (toxemia) of pregnancy, occuring in 25% of these pregnancies. symptoms malaise, nausea and/or vomiting, pain in the upper abdomen. edema Proteinuria Blood pressure may be elevated. Occasionally, coma can result from hypoglycemia Women with a history of HELLP syndrome increased risk for complications in future pregnancies MRI Courtesy Ashley Davidoff MD copyright 2008
|