Ascending pathways
Nociceptive input to the dorsal horn is relayed to higher centers via one of a number of ascending pathways.
Spinothalamic Tract
The spinothalamic tract is the most prominent ascending pathway for nociceptive neural transmission. Axons from WDR and NS neurons in laminae I and V decussate diagonally in the anterior white commissure before ascending in the contralateral anterolateral white matter, becoming the ascending projections of the neospinothalamic and paleospinothalamic tracts. As their names imply, the neospinothalamic tract is a phylogenetically younger system than the paleospinothalamic pathway. The neo-spinothalamic tract relays information concerning sharp pain that may be graded in intensity and localized to a specific region of the body. Axons of this tract terminate monosynaptically in the ventroposterolateral (VPL) nucleus of the thalamus. As such, information traveling this pathway is not modulated before arriving at the thalamus.
The majority of spinothalamic tract axons belong to the pa-leospinothalamic pathway. This pathway produces diffuse, aching pain that is difficult to localize but lets the body know that it must take action to avoid further injury. The paleospinothalamic tract sends multiple projections to the brain stem reticular formation in the medulla and pons and the medial thalamus before terminating in the VPL nucleus. A series of nuclei in the medulla and pons act to modify ascending nociceptive data in the pa-leospinothalamic tract. For instance, the locus ceruleus nucleus of the pons produces glutamate and serotonin precursors in response to fear or shock; these act to reduce the transmission of pain beyond the pons in acutely fear-producing situations (a mechanism of obvious survival value). The brain stem reticular formation also has extensive connections with a number of structures in the midbrain, including the periaqueductal gray matter, deep layers of the superior colliculus, the red nucleus, anterior and posterior pretectal nuclei, the nucleus of Darksche-witsch, and the interstitial nucleus of Cajal. These structures may act in conjunction with the reticular formation to further modulate data in the paleospinothalamic pathway.
Spinoreticular Tract
The spinoreticular tract is composed of axons of nociceptive neurons in laminae VII and VIII that ascend in the ipsilateral an-terolateral quadrant of the spinal cord, joining the spinothalamic tract in the medial lemniscus in the brain stem before terminating at many sites throughout the medullary, pontine, and mes-encephalic reticular formation. In addition, some axons send branches that terminate in both the reticular formation and the thalamus. Of note, some spinoreticular fibers do not cross the midline before terminating. Neurons of the reticular formation project, directly or indirectly, to many areas of the brain, including the thalamus, hypothalamus, limbic system, and neocortex.
Nociceptive data relayed to the reticular formation by the spi-noreticular tract contribute to the affective, motivational, and aversive response components of pain. This tract predates the more direct spinothalamic pathway in vertebrate evolution.
Spinomesencephalic Tract
This tract consists of nociceptive neurons originating in lamina I and laminae IV through VI that project to the mesencephalic reticular formation, the lateral portion of the periaqueductal gray region, the nucleus cuneiformis, the superior colliculus, and other sites in the midbrain. The periaqueductal region, in turn, has reciprocal connections with the limbic system via the hypothalamus.
The spinomesencephalic tract is involved in the production of fear and related affective and aversive behaviors associated with pain. The tract’s connections may also initiate orienting responses to noxious stimuli. Spinomesencephalic communication with the periaqueductal gray matter activates the system of descending pain modulation that subsequently produces endogenous analgesia.
Spinocervicothalamic Tract
Although most neurons in laminae III and IV of the dorsal horn respond solely to tactile stimuli, a minority respond to noxious stimuli as well. Spinocervicothalamic neurons project through the ipsilateral dorsolateral spinal cord to the lateral cervical nucleus in segments C1 and C2. Axons from this nucleus then decussate, ascending in the medial lemniscus in the brain stem to midbrain nuclei and to the ventroposterior lateral and posterior medial nuclei of the thalamus.
Postsynaptic Dorsal Column Fibers
Some nociceptive neurons in laminae III and IV project their axons in the dorsal column of the spinal cord to the cuneate and gracile nuclei in the medulla. Internal arcuate fibers then connect these nuclei with the contralateral VPL nucleus of the thalamus. Transmission of nociceptive data through the dorsal column in this fashion may be responsible for the persistence of painful symptoms after selective ablation of the spinothalamic tract (i.e., cordotomy). Stimulation of these fibers is a target for pain relief.
Visceral Nociceptive Tracts in Dorsal Columns
The dorsal columns of the spinal cord are primarily associated with discriminatory touch and proprioception; classically, they were not thought to be involved in pain transmission. However, a number of studies indicate that the dorsal columns have a role in the processing of visceral pain. In addition to relaying vis-cerosensory information, this pathway may also facilitate spinal neuronal sensitization of visceral origin; creation of dorsal column lesions reduced such sensitization in a model of chronic visceral pain. In a number of recent clinical studies, the creation of lesions in the dorsal columns resulted in good relief of visceral pain in cancer patients.
Spinohypothalamic Tract
The spinohypothalamic tract consists of a large number of neurons widely distributed throughout the spinal cord that communicate with the hypothalamus without synapse in the reticular formation. In addition, widespread collateral branching from spinohypothalamic tract neurons to a variety of targets in the medulla, pons, midbrain, and thalamus has been described. This pathway is involved in autonomic, neuroendocrine, and affective/emotional responses to noxious and other somatosensory stimuli of cutaneous or visceral origin. Some studies suggest that the majority of spinohypothalamic tract neurons respond exclusively or preferentially to noxious stimuli.
Thalamocortical Pathways
Thalamus The ascending pathways project directly or indirectly to a number of nuclei in both the lateral and medial thala-mus. In the lateral thalamus, the VPL nucleus is a main site of information relay from ascending pathways to the cortex. VPL neurons are primarily involved in sensory-discriminative aspects of pain perception, such as localization; however, the VPL may also be involved in visceral and referred pain. Neurons of the VPL nucleus, with receptive fields that are restricted in size, respond maximally to noxious mechanical stimuli; they also respond to noxious heat and C-fiber volleys. In addition, they respond weakly to nonnoxious mechanical stimuli. Most VPL neurons respond to both cutaneous and visceral stimuli; cutaneous input is soma-totopic, but visceral input is not similarly arranged. Almost all VPL neurons project to the primary somatosensory cortex.
In the medial thalamus, the spinothalamic tract projects to the central lateral nucleus and other intralaminar nuclei, as well as to the ventromedial preoptic nucleus (VMpo), whereas the spi-nomesencephalic and spinoreticular tracts project heavily to the intralaminar nuclei and other medial thalamic nuclei via the reticular formation. The medial thalamic nuclei appear to play their most significant role in processing the affective and motivational components of pain. Primate studies suggest that neurons of the intralaminar nuclei have large, bilateral receptive fields (presumably limiting their role in sensory discrimination, or at least in localization). VMpo neurons, which have small, somato-topically organized receptive fields, project to the insula, a fact that suggests they have a role in affective and motivational responses to pain, as well as memory processing.
Cortex There is still a great deal of uncertainty concerning cortical processing of pain. There is no single discrete cortical pain center. Indeed, imaging studies support activation of a number of cortical areas in response to painful stimuli, including the anterior cingular, insular, parietal, frontal, premotor, and primary and secondary somatosensory cortices.29 Patterns of cortical activation seen in experimentally induced pain may not match those seen in chronic pain, however.30 Positron emission tomography studies have associated experimentally induced pain with increased regional cerebral blood flow to the bilateral anterior insular and posterior parietal cortices, bilateral inferior lateral prefrontal cortices, and cerebellar vermis and decreased blood flow to the contralateral posterior thalamus.29
The preponderance of imaging studies that associate activity in the anterior cingulate cortex (ACC) with both pain and behavioral drive and volition support a primary role for this region in the cortical processing of the motivational and affective components of pain. The critical role of the ACC in processing nocicep-tive data has raised interest in this cortex as a target of neuroab-lative therapy for intractable pain.31 The anterior cingulate cortex, a major destination of outflow from the medial thalamus, is selectively activated by painful thermal stimuli and appears to be important in the processing of affective components of the pain experience.
Lesion studies suggest that large areas of damage to the so-matosensory cortex do not yield impaired response to noxious stimuli. Cortical stimulation in general is only infrequently associated with the production of pain; large lesions of the so-matosensory cortex may produce minimal or no pain, whereas small lesions elsewhere in the cortex may be associated with spontaneous pain or increased pain perception.32
Descending pathways
The perception of pain at higher levels of the CNS triggers activation of descending pain suppression pathways involving numerous cortical and subcortical structures, as well as a variety of neurotransmitters.33,34 The existence of such descending pathways was first suggested by the finding that brain stem stimulation inhibited nociceptive neurons in the dorsal horn of the spinal cord, but such suppression was negated by lesions of the dorsolateral funiculus. Neurons in the midbrain periaqueductal gray matter (PAG) and periventricular gray matter make excitatory connections to the nucleus raphe magnus (NRM) and the adjacent nucleus reticularis paragigantocellularis in the rostro-ventral medulla, as well as the locus ceruleus, among other nuclei. Neurons from these regions, especially the NRM and adjacent reticular formation, then make inhibitory connections in laminae I, II, and V of the dorsal horn. Thus, stimulation of PAG and subsequent stimulation of rostroventral medullary neurons lead to inhibition of dorsal horn neurons that transmit nocicep-tive data. Neurotransmitters involved in this pathway include endogenous opiates, serotonin, and norepinephrine. Noradre-nergic projections from the dorsolateral pons to the dorsal horn of the spinal cord, relayed through the raphe magnus and pal-lidus, PAG, and ventrolateral reticular formation, constitute another significant antinociceptive pathway. Studies of stimulation-invoked analgesia also support roles for neurons of the reticular formation and anterior pretectal nucleus in descending antinociception. Stimulation of the VPL or ventroposteromedial thalamic nuclei leads to reduction in severity of several painful syndromes. Inhibition of spinothalamic tract neurons secondary to thalamic stimulation may result from antidromic activation of axons of spinothalamic tract neurons sending collaterals to brain stem nuclei such as the PAG. As described, sensory and descending neurons and interneurons converge in the dorsal horn of the spinal cord. These local circuits play a significant role in modulating descending pathway activity.
Endogenous opiates include enkephalins, dynorphins, and endorphins. Enkephalins and dynorphins are found in the PAG and rostroventral medulla, as well as in the dorsal horn of the spinal cord (especially laminae I and II). ^-Endorphins are found in hypothalamic neurons that project to the PAG and noradre-nergic nuclei in the brain stem.
Three major classes of opiate receptors are found in the descending pain suppression pathways and are widely distributed throughout the CNS. Enkephalins are active at the mu and delta receptors, whereas dynorphin is active at the kappa receptor. The primary classes of opiate receptors may be further subdivided into distinct subtypes. The different receptor classes may modulate the activity of different types of nociceptive inputs.
Opiate alkaloids such as morphine are potent agonists of the mu receptor, found in high concentration in the PAG and the superficial dorsal horn of the spinal cord. Opiates act at supra-spinal levels (i.e., the raphe nuclei and PAG) to suppress GABA-releasing interneurons that normally inhibit descending pathway activity. This disinhibitory mechanism thus serves to activate the descending pain suppression pathways. Opiates also exhibit analgesic activity at the level of the primary afferent synapse in the dorsal horn of the spinal cord. The superficial dorsal horn has a large number of enkephalin- and dynorphin-con-taining interneurons. Mu opiate receptors are located on the terminals of nociceptive afferents and the dendrites of postsynaptic dorsal horn neurons.
Opiate alkaloids and endogenous opioid peptides act pre-synaptically to suppress neurotransmitter release from sensory neurons. They also act postsynaptically to suppress the activity of the nociceptive dorsal horn neurons. That opioid receptors are ubiquitous throughout the CNS suggests that modulation of nociceptive data may occur at multiple sites, in addition to the aforementioned descending pathways and dorsal horn.
Neurobiology of Specific Pain Types
Cancer pain
Approximately 70% to 90% of patients with advanced cancer have chronic pain; pain is directly related to the presence of primary or metastatic cancer in up to three quarters of these patients.35 Although cancer pain may involve any tissue, certain pain syndromes are commonly seen in the setting of malignant disease. Common mechanisms for cancer-related pain include direct effects of tumor growth, visceral involvement, bony metastases, soft tissue invasion, and nerve infiltration or compression. Exposition of the full range of cancer-related pain is beyond the scope of this topic; some of the more common or significant syndromes are discussed.
Bone Pain
Tumor involvement of bone is the most frequent cause of cancer pain. Multiple myeloma and metastatic disease of the breast, lung, thyroid, and prostate are the cancers that most commonly involve bone. Different tumor types may produce primarily lytic or blastic metastases, but the majority result in mixed lesions. Osteoclast-mediated destruction of bone appears to be an important mechanism of pain in malignant disease. Tumors may also cause bone pain via ischemia, pressure, or secretion of chemical mediators. Pathologic fracture secondary to significant infiltration of bone may lead to an acute increase in pain severity, as well as neural impingement or compression. Metastasis to the vertebral column (see below) may lead to a wide variety of pain symptoms. Although the clinical experience of pain will vary with the mechanisms of the pain, most cancer-related bone pain is described as focal and constant, increasing in severity over time with progression of disease.
Plexopathy
A number of plexopathies are seen in cancer patients. Brachial plexopathy secondary either to metastasis or to tumor spread from lymphoma or from lung, breast, or thyroid cancer is a common cause of rapidly progressive arm or shoulder pain in cancer patients. Horner syndrome may also be seen in this setting. Brachial plexopathy may also result from radiotherapy (see below). Cervical plexopathy results from malignant invasion of the cervical plexus by head and neck tumors and produces pain in the ear or neck. Lumbosacral plexopathy may produce some combination of local, referred, or radicular pain in the low back, abdomen, perineum, or leg.
Back Pain
The prevalence of back pain in cancer is not known, but one large series found that it was the most common neurologic symptom in patients with a history of systemic cancer.36 Back pain in this setting is typically from bone or epidural metastases; up to one third of cancer patients may develop metastases to the spine, with the thoracic vertebral column being the most frequent site of bony metastases. Acutely worsening back pain or increasing neurologic symptoms may indicate involvement of the spinal cord or one or more nerve roots. Any patient with a history of cancer who complains of back pain must be evaluated emergently to rule out epidural spinal cord compression [see 12:XIl Oncologic Emergencies]. Less commonly, back pain may be caused by retroperitoneal tumors.
Headache
Estimates of the prevalence of headache in patients with brain tumors vary widely, from 8% to 71%.37 Infratentorial and intraventricular tumors, multiple metastases, and leptomeningeal carcinomatosis are most commonly associated with cancer-related headache. Headache in the setting of brain tumor is generally from traction on and displacement of intracranial pain-sensitive structures, such as cranial and cervical nerves, blood vessels, and dura. Pain may also arise from inflammation or direct infiltration of those structures. It may also occur as the result of disturbance or obstruction of the flow of cerebrospinal fluid; sagittal sinus occlusion; stroke; or other causes. Cancer-related headache pain is variable in presentation but is most often described as being of mild or moderate intensity, lasting for hours, possibly developing over weeks or months, and possibly associated with nausea, vomiting, mental status changes, or focal neurologic findings. Forsyth and colleagues reported that patients with a history of headache who develop brain tumors are more likely to complain of headache as their primary presenting tumor symptom than patients without a history of headache.38 These data underscore the critical importance of a comprehensive neurologic assessment in all patients presenting with headache.
Abdominal Pain
Primary or metastatic intra-abdominal malignancy may cause poorly localized visceral pain, sometimes with associated nausea, vomiting, or systemic symptoms. Causes of pain include direct invasion of tissue, peritoneal inflammation, and vascular or lymphatic obstruction. Pain secondary to abdominal cancers may be referred elsewhere, as when diaphragmatic irritation results in shoulder pain. Alternatively, pain from spinal malignancy may be referred to the abdomen.
Latrogenic Pain
Many of the diagnostic and therapeutic modalities utilized in the care of cancer patients can result in pain.35 Radiotherapy is associated with such painful conditions as osteonecrosis, acute and chronic enteritis, mucositis, and brachial plexopathy. Chemo-therapeutic agents may produce painful neuropathies, as well as a variety of distressing side effects. Steroid therapy may lead to avascular necrosis, as well as to ultimately painful consequences of immunosuppression. Preparation for bone marrow or stem cell transplantation leads to mucositis in 70% of patients. Pain after cancer surgeries may be severe. In addition, chronic pain syndromes have been identified after mastectomy, thoracotomy, amputation, and radical neck dissection. Surgery for abdominal malignancies may lead to adhesions and subsequent painful bowel obstruction. Common hospital procedures may also be a significant source of pain and distress.
HIV infection and aids pain
HIV infection and AIDS can lead to pain through numerous distinct pathophysiologic mechanisms. Pain in this setting may be attributable to the direct neurotoxic effects of HIV on central or peripheral nerves, opportunistic infection or malignancy secondary to immunosuppression, or medication side effects. In one survey, 67% of AIDS patients reported pain in the previous 4 weeks39; many pain syndromes in ambulatory AIDS patients are directly related to infection or other consequences of immunosup-pression. Most underlying causes of pain in AIDS are treatable.
HIV-associated peripheral neuropathy is the most frequent neurologic complication of AIDS, affecting almost one third of patients with the disease.40 Distal symmetrical polyneuropathy (DSP), the most common form, is characterized by paresthesias, dysesthesias, or numbness occurring in a stocking-and-glove distribution. Distal pain, often described as sharp, stabbing, or burning, may become excruciating. DSP is seen primarily in advanced disease or secondary to antiretroviral treatment. Clinically, DSP caused by HIV infection is indistinguishable from DSP caused by antiretroviral agents, except for the latter’s response to reduction or withdrawal of antiretroviral agents. Acute inflammatory demyelinating polyneuropathy (AIDP), characterized by muscle weakness, tingling, and ascending paralysis, may be the initial manifestation of HIV infection. Chronic inflammatory de-myelinating polyneuropathy, a chronic form of AIDP marked by reduced reflexes and patchy weakness or numbness, may develop at seroconversion or a later stage of disease. Progressive polyneuropathy is characterized by rapidly progressive flaccid paraparesis, subacute low back and radicular pain and paresthe-sias, areflexia, and sphincter dysfunction. Most often, it is secondary to cytomegalovirus infection; it is observed most frequently in advanced HIV disease. Mononeuropathy multiplex occurring in early HIV disease is marked by self-limited sensory and motor deficits in the distribution of individual peripheral nerves; in advanced disease, multiple nerves in multiple extremities or cranial nerves may be involved. In mononeuropathy multiplex secondary to vasculitis, pain will precede sensory and motor deficits. Diffuse infiltrative lymphocytosis syndrome (DILS) is a subacute, often painful, distal sensorimotor neuropathy associated with parotid enlargement and sicca syndrome; there is sometimes systemic involvement (i.e., lymphadenopa-thy, splenomegaly, or interstitial pneumonia). DILS may occur during symptomatic HIV infection.
Pain Management
Barriers to effective pain management
Undertreatment of pain remains a significant clinical problem. SUPPORT found that 50% of adults dying in the hospital experienced moderate to severe pain in the period immediately before death.16 In one large multicenter study, 86% of physicians felt that the majority of their patients with pain were undertreat-ed.8 The preponderance of studies suggest that most cancer patients do not receive adequate pain relief.
A number of barriers to effective pain management relate to health care delivery systems. Most health care organizations have not implemented procedures to ensure accountability for adequate assessment and treatment of pain. Many organizations fail to make pain relief a visible priority through such measures as adoption of standardized protocols or provision of sufficient time for training. Fragmentation of patient care across multiple clinical settings increases the likelihood of poor care. Use of gatekeepers and an emphasis on cost control by managed care organizations provide further systemic disincentives for the treatment of pain. Restrictive laws governing the use of controlled substances may have a significant effect on analgesic prescribing patterns. Clinician pain management practices are likely influenced by concerns about licensing, state disciplinary actions, and legal penalties arising from opioid prescribing patterns.
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Table 1 Principles of Pain Assessment |
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1. Believe the patient’s complaint of pain |
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2. Take a careful pain history |
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Onset |
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Temporality |
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Location |
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Quality (sensory versus affective) |
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Intensity |
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Aggravating/relieving factors |
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Associated symptoms |
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3. List and prioritize each pain complaint |
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4. Evaluate the response to current and previous treatment approaches |
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5. Evaluate the patient’s psychological state |
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6. Assess patient function |
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7. Ask about a history of alcohol or drug dependence |
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8. Consider relevant past medical history |
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9. Perform a comprehensive medical and neurologic examination |
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10. Order and review appropriate diagnostic procedures |
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11. Make relevant referrals for multidisciplinary assessment |
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12. Assess patient expectations and goals |
Several barriers center on physician attitudes or practices. A paucity of time devoted to the subject in the curricula of most United States medical schools and residencies has led to deficiencies in the pain management skills of many clinicians. In one study of physician attitudes regarding cancer pain, inadequate assessment skills were identified most frequently as a significant impediment to effective pain relief.8 In another study, 70% to 80% of neurologists did not feel adequately trained to diagnose or treat patients with pain.41 Some physicians are reluctant to prescribe opioids in any setting other than end-stage terminal illness. Clinician discomfort with opioid use is multifactorial; sources of unease include inadequate knowledge of opioid management, fear of patient addiction, and fear of professional censure or legal penalties for excessive use of these analgesics. Some clinicians do not view pain relief as central to the treatment of disease, or they may have low expectations regarding adequate pain relief. Physicians may not accept patient self-reports of pain as reliable.
Other barriers relate to patients’ attitudes. Patients may be reluctant to report pain for any of a number of reasons. They may fear appearing "difficult" or "problematic," or they may have low expectations of obtaining relief. Alternatively, they may deny pain because of fear of its potential implications for their underlying illness. Patients may be reluctant to take prescribed opioids because of concerns about addiction or drug side effects. Patients with chronic pain may cease seeking medical treatment out of frustration with previous unsuccessful attempts at pain relief. In a survey of parents of children who had died of cancer, the parents reported overall satisfaction in the care their children received despite noting that pain was inadequately controlled.42
Financial and cultural barriers may also prevent effective pain management in some populations.
Principles of pain assessment
Accurate pain assessment is the necessary precursor to effective pain management. At least one large multicenter study named inadequate pain assessment skills as the most frequent barrier to the provision of effective pain care.8 Adherence to the following principles of pain assessment will greatly improve the treatment of pain [see Table 1].43
• Believe the patient’s complaint of pain. Accepting that a patient’s complaint is real and therefore deserving of further investigation is the logical prerequisite to further effective pain assessment. The patient’s self-report is the single most accurate indicator of the existence and severity of pain. Fear of drug-seeking may predispose some physicians to disbelieve the pain complaints of some patients. However, lack of trust is associated with poor pain management and corresponding poor outcomes.
• Take a careful pain history. As with the medical workup of any complaint, a thorough history of the present illness is necessary. Specific areas to evaluate include the following.
Pain onset When did the pain begin? Was the onset spontaneous or gradual? Was there a possible precipitating event (e.g., trauma or surgery)? If so, the physician should obtain relevant details of the precipitating event (e.g., the nature and extent of trauma, any treatment at time of trauma). Did the patient ever experience similar pain?
Temporality What is the duration of the pain? Is it chronic, episodic, or intermittent? Is it acute or subacute? Is breakthrough pain experienced? Is it incidental?
Location Where is the pain? Is it in one or multiple locations? Does it radiate? Does the location of pain vary?
Quality What does the pain feel like? What word or words are used to describe the pain (e.g., sharp, dull, burning)? Adjectives chosen often fall into two broad categories: sensory, in which pain is described in essentially physical terms; and affective, in which the pain experience may have a significant emotional component. Particular words chosen may also provide important clues to the etiology of pain (e.g., neuropathic versus musculoskeletal).
Intensity Pain may be measured by use of a variety of scientifically validated assessment tools.44 The Numeric Pain Intensity Scale, in which the patient rates his or her pain on a scale from zero to ten (0 = no pain, 10 = worst pain imaginable), allows for quantification of pain severity, evolution over time, and response to treatment. Use of the Visual Analog Scale or the Simple Descriptive Pain Intensity Scale may be better for some patient populations. In the Visual Analog Scale, a mark on a horizontal line denotes pain intensity; in the Simple Descriptive Pain Intensity Scale, the patient picks an appropriate verbal pain descriptor. The Faces Pain Scale for Adults and Children and the Wong-Baker Faces Rating Scale consist of multiple faces with various expressions; the patient may select the facial expression most consistent with his or her current level of pain. This methodology has been validated for use in the pediatric population. Several more extensive tools for assessing pain and its impact on the activities of daily living, such as the Initial Pain Assessment Tool, Brief Pain Inventory, McGill Pain Questionnaire, Memorial Pain Assessment Card, Neuropathic Pain Scale, and Memorial Symptom Assessment Scale [see CE:X Symptom Management in Palliative Medicine], permit valid serial assessment of pain and its functional import. For general clinical practice, however, simple assessment tools are sufficient.
Aggravating or relieving factors What exacerbates the pain? What relieves it?
Associated symptoms Is the patient experiencing any other symptoms, such as nausea, vomiting, diarrhea, or anorexia? Such symptoms may relate to the pain itself or to an underlying disease process.
• List and prioritize each pain complaint. Prioritization of multiple pain complaints should be based primarily on the patient’s subjective ranking of significance.
• Evaluate the response to current and previous treatment approaches. What is being done for pain relief at present? What pharmacologic or other therapeutic approaches have been attempted in the past? Were adequate trials of medications given? Were these approaches successful? Has the patient experienced adverse events associated with pain management modalities?
• Evaluate the patient’s psychological state. Consideration of psychological and psychosocial factors should start at the time of initial pain assessment and continue throughout treatment. Are there any recent sources of stress (e.g., marital or vocational problems)? Has the pain affected the patient’s mood? Is the patient suffering from any psychiatric illness? Is this illness treated or untreated? Certain psychiatric conditions, such as depression, anxiety, and posttraumatic stress disorder, frequently coexist with chronic pain and may have significant somatic components. Clinical depression may have a profound influence on the patient’s perception of pain and on the patient’s ability to comply with subsequent treatment. Thus, simultaneous treatment of psychiatric pathology may be an integral part of the pain management plan. Depression and anxiety may lead to somatic complaints, and untreated pain may exacerbate depression and anxiety. Instruments such as the Medical Outcomes Study 36-Item Short Form (SF-36) and the Sickness Impact Profile may be used to assess the broader impact of pain on quality of life, including social, psychological, and spiritual well-being; these instruments are available through the Medical Outcomes Trust (http://www.outcomes-trust.org/instruments.htm). The patient’s mental status should also be assessed. Cognitively impaired patients can sometimes give reliable reports of pain, but other assessment tools may be needed. Obtaining a history from family members, friends, or both is critical in caring for such patients.
• Assess patient function. How has the pain affected work, family, or social responsibilities or relationships? Have activities of daily living been impaired? What (if any) important activities is the patient unable to perform? Is the patient eating and sleeping as he or she did before the pain? In the case of chronic pain, what support structures does the patient have? The Wisconsin Brief Pain Questionnaire, or Brief Pain Inventory (http://www.stat.washington.edu/TALARIA/attachb1.html), is one of the instruments that may be used to evaluate the effect of pain on various domains of function.
• Evaluate for a history of alcohol or drug dependence. Previous or current substance abuse or dependence may impact the patient’s compliance with analgesic regimens, psychological state, function, and other domains. Ensuring the safety of the patient in the community when considering prescribing potent analgesic medication is of paramount importance [see 13:VI Drug Abuse and Dependence].
• Consider relevant past medical history. Many acute and chronic conditions may present as or eventually lead to pain; these include diabetes, coronary artery disease, malignancy, and the various chronic pain syndromes. A comprehensive medical history may provide important cues for treatment.
• Perform a comprehensive medical and neurologic examination. Performance of a physical examination will, at the very least, reassure the patient that his or her complaint is being taken seriously. The examination may also reveal the pathologic basis of pain. Often, the revealed disease process is unsuspected; in one study, pain consultants discovered a previously undiagnosed cause of pain in 64% of patients seen.45 The examiner should look for any pain behaviors (e.g., abnormal gait or posture, guarding) and interpret their presence or absence in terms of the patient’s overall presentation and social interaction. Observation for signs of systemic illness should accompany a detailed evaluation of reported pain sites. Every patient with a complaint of pain should, at minimum, undergo a neurologic examination. Chronic pain is often a sequela of neurologic pathology, and such patients are best cared for within a neurologic framework.
• Order and review appropriate diagnostic procedures. Although the diagnosis of painful conditions is usually made on the basis of the history and physical examination, and pain per se is not identifiable by any diagnostic modality, imaging and other studies such as laboratory tests, electromyelogra-phy, nerve conduction studies, or diagnostic nerve blocks may be valuable in the assessment of disease processes that can give rise to pain. Certain disease-specific laboratory measurements (e.g., tumor markers in some malignancies) are sensitive indicators of disease progression and may correlate with painful symptoms. Findings on imaging studies do not correlate, or correlate weakly, with patient pain experiences.
• Make relevant referrals for multidisciplinary assessment. Many painful conditions may be managed adequately by a patient’s primary care physician. However, referral to a pain specialist or a team approach may be best for certain cases of chronic, cancer-related, or otherwise complex pain that is debilitating or refractory to treatment. Important members of the pain management team may include neurologists, psychiatrists, anesthesiologists, physiatrists, physical or occupational therapists, clergy, social workers, and counselors. Pain clinics may bring all relevant team members "under one roof." Many pain specialists believe that referrals frequently are made past the so-called golden hour when their intervention may be of maximal effectiveness, especially in cases of neuropathic and cancer pain. Referral to a pain specialist ideally should occur before significant disability or loss of function occurs; pain behaviors or the emergence of maladaptive coping strategies may serve as cues for referral.
• Assess patient expectations and goals. What does the patient expect or hope for in terms of treatment outcomes? Patient goals should be assessed in a number of domains, including pain intensity, daily function, and quality of life. Having patients set goals will keep the physician from taking a narrow focus on physical factors such as pain intensity, to the exclusion of the larger aspects of pain’s impact on the patient’s life.
