Transduction.

Transduction involves the conversion of a noxious mechanical, thermal, or chemical stimulus into an electrical signal called an action potential. Noxious (tissue-damaging) stimuli, including thermal (e.g., sunburn), mechanical (e.g., surgical incision), or chemical (e.g., toxic substances) stimuli, cause the release of numerous chemicals such as hydrogen ions, substance P, and adenosine triphosphate (ATP) into the damaged tissues. Other chemicals are released from mast cells (e.g., serotonin, histamine, bradykinin, prostaglandins) and macrophages (e.g., interleukins, tumor necrosis factor [TNF]). These chemicals activate nociceptors, which are specialized receptors, or free nerve endings, that respond to painful stimuli. Activation of nociceptors results in an action potential that is carried from the nociceptors to the spinal cord primarily via small, rapidly conducting, myelinated A-delta fibers and slowly conducting unmyelinated C fibers.

In addition to stimulating nociceptors to fire, inflammation and the subsequent release of chemical mediators lower nociceptor thresholds. As a result, nociceptors may fire in response to stimuli that previously were insufficient to elicit a response. They may also fire in response to non-noxious stimuli, such as light touch. This increased susceptibility to nociceptor activation is called peripheral sensitization. Leukotrienes, prostaglandins, cytokines, and substance P are involved in peripheral sensitization. Cyclooxygenase (COX), an enzyme produced in the inflammatory response, also plays an important role in peripheral sensitization. A clinical example of this process is sunburn. This thermal injury causes inflammation that results in a sensation of pain when the affected skin is lightly touched. Peripheral sensitization also amplifies signal transmission, which in turn contributes to central sensitization (discussed under Dorsal Horn Processing). The pain produced from activation of peripheral nociceptors is called nociceptive pain (described later in the chapter on p. 119).

Therapies that alter either the local environment or sensitivity of the peripheral nociceptors can prevent transduction and initiation of an action potential. Decreasing the effects of chemicals released at the periphery is the basis of several drug approaches to pain relief. For example, nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin) and naproxen (Naprosyn, Aleve), and corticosteroids, such as dexamethasone (Decadron), exert their analgesic effects by blocking pain-sensitizing chemicals. NSAIDs block the action of COX, thereby interfering with the production of prostaglandins. Corticosteroids reduce the production of both prostaglandins and leukotrienes (see Fig. 12-2).

Drugs that stabilize the neuronal membrane and inactivate peripheral sodium channels inhibit production of the nerve impulse. These medications include local anesthetics (e.g., injectable or topical lidocaine, bupivacaine [Sensorcaine], and ropivacaine [Naropin]) and antiseizure drugs (e.g., carbamazepine [Tegretol] and lamotrigine [Lamictal]).

Transmission.

Transmission is the process by which pain signals are relayed from the periphery to the spinal cord and then to the brain. The nerves that carry pain impulses from the periphery to the spinal cord are called primary afferent fibers. These include A-delta and C fibers, each of which is responsible for a different pain sensation. As previously mentioned, A-delta fibers are small, myelinated fibers that conduct pain rapidly and are responsible for the initial, sharp pain that accompanies tissue injury. C fibers are small, unmyelinated fibers that transmit painful stimuli more slowly and produce pain that is typically aching or throbbing in quality. Primary afferent fibers terminate in the dorsal horn of the spinal cord. Activity in the dorsal horn integrates and modulates pain inputs from the periphery.

The propagation of pain impulses from the site of transduction to the brain is shown in Fig. 9-1. Three segments are involved in nociceptive signal transmission: (1) transmission along the peripheral nerve fibers to the spinal cord, (2) dorsal horn processing, and (3) transmission to the thalamus and the cerebral cortex.

Dorsal Horn Processing.

Once a nociceptive signal arrives in the spinal cord, it is processed within the dorsal horn. Neurotransmitters released from the afferent fiber bind to receptors on nearby cell bodies and dendrites of cells. Some of these neurotransmitters (e.g., glutamate, aspartate, substance P) produce activation, whereas others (e.g., γ-aminobutyric acid [GABA], serotonin, norepinephrine) inhibit activation of nearby cells. In this area, exogenous and endogenous opioids also play an important role by binding to opioid receptors and blocking the release of neurotransmitters, particularly substance P. Endogenous opioids include enkephalin and β-endorphin. They are capable of producing analgesic effects similar to those of exogenous opioids such as morphine.

Increased sensitivity and hyperexcitability of neurons in the CNS is called central sensitization. Peripheral tissue damage or nerve injury can cause central sensitization, and continued nociceptive input from the periphery is necessary to maintain it. As a result of the increased excitability of neurons within the CNS, normal sensory inputs cause abnormal sensing and responses to painful and other stimuli. This explains why some people experience significant pain from touch or tactile stimulation in and around the areas of tissue or nerve injury. This is called allodynia. With central sensitization, the central processing circuits are altered. In some cases, central sensitization can be long-lasting due to changes in the synapse.¹⁰

With ongoing stimulation of slowly conducting unmyelinated C-fiber nociceptors, firing of specialized dorsal horn neurons gradually increases. These inputs create many problems, including the sprouting of wide dynamic range (WDR) neurons and induction of glutamate-dependent N-methyl-d-aspartate (NMDA) receptors. WDR neurons respond to both nociceptive and non-nociceptive inputs that are of varying levels of stimulus intensity. When these neuron dendrites sprout, they grow into areas where pain-receiving nerve cell bodies are located. This results in the capacity to transmit a broader range of stimuli-producing signals, which are then passed up the spinal cord and brain. This process is known as windup and depends on the activation of NMDA receptors. NMDA receptor antagonists, such as ketamine (Ketalar), potentially interrupt or block mechanisms that lead to or sustain central sensitization. Windup, like central sensitization and hyperalgesia (increased pain responses to noxious stimuli), is induced by C-fiber inputs. Windup is different, however, in that it can be short lasting, whereas central sensitization and hyperalgesia persist over time.¹¹

It is important for you to understand that acute, unrelieved pain leads to chronic pain through the process of central sensitization. Acute tissue injury produces a cascade of events that involve the release of certain excitatory neurotransmitters (e.g., glutamate) and neuropsychologic responses. Even brief intervals of acute pain are capable of inducing long-term neuronal remodeling and sensitization (plasticity), chronic pain, and lasting psychologic distress.

Neuroplasticity refers to processes that allow neurons in the brain to compensate for injury and adjust their responses to new situations or changes in their environment.¹² Neuroplasticity contributes to adaptive mechanisms for reducing pain but also can result in maladaptive mechanisms that enhance pain. Genetic variability among individuals may have an important effect on the plasticity of the CNS.¹² Understanding this phenomenon helps explain individual differences in response to pain and why some patients develop chronic pain conditions whereas others do not. Clinically, central sensitization of the dorsal horn results in (1) hyperalgesia, (2) painful responses to normally innocuous stimuli (allodynia), (3) prolonged pain after the original noxious stimulus ends (called persistent pain), and (4) the extension of tenderness or increased pain sensitivity outside of an area of injury to include uninjured tissue (i.e., expansion of nociceptive receptive fields, or secondary hyperalgesia).¹³

Referred pain must be considered when interpreting the location of pain reported by the person with an injury or a disease involving visceral organs. The location of a stimulus may be distant from the pain location reported by the patient (Fig. 9-2). For example, pain from liver disease is frequently located in the right upper abdominal quadrant, but can also be referred to the anterior and posterior neck region and to a posterior flank area. If referred pain is not considered when evaluating a pain location report, diagnostic tests and therapy could be misdirected.

Perception.

Perception occurs when pain is recognized, defined, and assigned meaning by the individual experiencing the pain. In the brain, nociceptive input is perceived as pain. There is no single, precise location where pain perception occurs. Instead, pain perception involves several brain structures. For example, it is believed that the reticular activating system (RAS) is responsible for warning the individual to attend to the pain stimulus; the somatosensory system is responsible for localization and characterization of pain; and the limbic system is responsible for the emotional and behavioral responses to pain. Cortical structures also are crucial to constructing the meaning of the pain.

Therefore behavioral strategies such as distraction and relaxation are effective pain-reducing therapies for many people. By directing attention away from the pain sensation, patients can reduce the sensory and affective components of pain. Opioids and other classes of analgesics such as some types of antiseizure drugs and antidepressants modify pain perception.

Modulation.

Modulation involves the activation of descending pathways that exert inhibitory or facilitatory effects on the transmission of pain (see Fig. 9-1). Depending on the type and degree of modulation, nociceptive stimuli may or may not be perceived as pain. Modulation of pain signals can occur at the level of the periphery, spinal cord, brainstem, and cerebral cortex. Descending modulatory fibers release chemicals such as serotonin, norepinephrine, GABA, and endogenous opioids that can inhibit pain transmission.

Several antidepressants exert their effects through the modulatory systems. For example, tricyclic antidepressants (e.g., amitriptyline [Elavil]) and serotonin norepinephrine reuptake inhibitors (SNRIs) (e.g., venlafaxine [Effexor] and duloxetine [Cymbalta]) are used in the management of chronic nonmalignant and cancer pain. These agents interfere with the reuptake of serotonin and norepinephrine, thereby increasing their availability to inhibit noxious stimuli.

Pain Pattern.

Assessing pain onset involves determining when the pain started. Patients with acute pain resulting from injury, acute illness, or treatment (e.g., surgery) typically know exactly when their pain began. Those with chronic pain may be less able to identify when the pain started. Establish the duration of the pain (how long it has lasted). This information helps to determine whether the pain is acute or chronic and assists in identifying the cause of the pain. For example, a patient with advanced cancer who also has chronic low back pain from spinal stenosis reports a sudden, severe pain in the back that began 2 days ago. Knowing the onset and duration can lead to a diagnostic workup that may reveal new metastatic disease in the spine.

Pain pattern also provides clues about the cause of the pain and directs its treatment. Many types of chronic pain (e.g., arthritis pain) increase and decrease over time. A patient may have pain all the time (constant, around-the-clock pain), as well as discrete periods of intermittent pain.

Breakthrough pain (BTP) is transient, moderate to severe pain that occurs in patients whose baseline persistent pain is otherwise mild to moderate and fairly well controlled. The average peak of BTP can be 3 to 5 minutes, and can last up to 30 minutes or even longer. BTP can either be predictable or unpredictable, and patients can have one to many episodes per day. Several transmucosal fentanyl products are specifically used to treat BTP.

End-of-dose failure is pain that occurs before the expected duration of a specific analgesic. It should not be confused with BTP. Pain that occurs at the end of the duration of an analgesic often leads to a prolonged increase in the baseline persistent pain. For example, in a patient on transdermal fentanyl (Duragesic patches) the typical duration of action is 72 hours. An increase in pain after 48 hours on the drug would be characterized as end-of-dose failure. End-of-dose failure signals the need for changes in the dose or scheduling of the analgesic. Episodic, procedural, or incident pain is a transient increase in pain that is caused by a specific activity or event that precipitates pain. Examples include dressing changes, movement, position changes, and procedures such as catheterization.

Location.

Determining the location of pain assists in identifying possible causes and treatment. Some patients may be able to specify the precise location(s) of their pain, whereas others may describe general areas or comment that they “hurt all over.” The location of the pain may also be referred from its origin to another site (see Fig. 9-2). For example, myocardial infarction can result in pain in the left shoulder. Pain may also radiate from its origin to another site. For example, angina pectoris can radiate from the chest to the jaw or down the left arm. This is referred to as radiating pain. Sciatica is pain that follows the course of the sciatic nerve. It may originate from joints or muscles around the back or from compression or damage to the sciatic nerve. The pain is projected along the course of the peripheral nerve, causing painful shooting sensations down the back of the thigh and inside of the leg to the foot.

Obtain information about the location of pain by asking the patient to (1) describe the site(s) of pain, (2) point to painful areas on the body, or (3) mark painful areas on a pain map (see eFig. 9-2, available on the website for this chapter). Because many patients have more than one site of pain, make certain that the patient describes every location.

Intensity.

Assessing the severity, or intensity, of pain provides a reliable measure to determine the type of treatment and its effectiveness. Pain scales help the patient communicate pain intensity. Choice of a scale to use should be based on the patient’s developmental needs and cognitive status. Most adults can rate the intensity of their pain using numeric scales (e.g., 0 = no pain, 10 = the worst pain) or verbal descriptor scales (e.g., none, a little, moderate, severe). These tools are sometimes easier for patients to use if they are oriented vertically or include a visual component. The Pain Thermometer Scale is an example of this type of scale¹⁵ (Fig. 9-3). Other visual pain measures or scales include the Wong-Baker FACES Pain Rating Scale (see eFig. 9-3 on the website for this chapter) and the FACES Pain Scale–Revised (see eFig. 9-4 on the website for this chapter). These and other pain scales may be useful for patients with cognitive or language barriers to describe their pain.¹⁶ Pain assessment measures for cognitively impaired adults and nonverbal adults are addressed later in this chapter.

Although intensity is an important factor in determining analgesic approaches, do not dose patients with opioids solely based on reported pain scores.¹⁷ Opioid “dosing by numbers” without taking into account a patient’s sedation level and respiratory status can lead to unsafe practices and serious adverse events. Safer analgesic administration can be achieved by balancing an amount of pain relief with analgesic side effects. Adjustments in therapy can be made to promote better pain control and minimize adverse outcomes.

Quality.

The pain quality refers to the nature or characteristics of the pain. For example, patients often describe neuropathic pain as burning, numbing, shooting, stabbing, electric shock–like, or itchy. Nociceptive pain may be described as sharp, aching, throbbing, dull, and cramping. Since the quality of pain relates to some degree to the classification of pain (e.g., neuropathic, nociceptive, or visceral), these descriptors can help to guide treatment options that best address the specific mechanism of pain.

Associated Symptoms.

Associated symptoms such as anxiety, fatigue, and depression may exacerbate or be exacerbated by pain. Ask about activities and situations that increase or alleviate pain. For example, musculoskeletal pain may be increased or decreased with movement and ambulation. Resting or immobilizing a painful body part can decrease pain. Knowing what makes pain better or worse can help characterize the type of pain and be helpful in selecting treatments.

Management Strategies.

As people experience and live with pain, they may cope differently and be more or less willing to try different strategies to manage it. Some strategies are successful, whereas others are not. To maximize the effectiveness of the pain treatment plan, ask patients what they are using now to control pain, what they have used in the past, and the outcomes of these methods. Strategies include prescription and nonprescription drugs and nondrug therapies such as hot and cold applications, complementary and alternative therapies (e.g., herbal products, acupuncture), and relaxation strategies (e.g., imagery). It is important to document both those that work and those that are ineffective.

Impact of Pain.

Pain can have a profound influence on a patient’s quality of life and functioning. In your assessment, include the effect of the pain on the patient’s ability to sleep, enjoy life, interact with others, perform work and household duties, and engage in physical and social activities. Also assess the impact of pain on the patient’s mood.

Patient’s Beliefs, Expectations, and Goals.

Patient and family beliefs, attitudes, and expectations influence responses to pain and pain treatment. Assess for attitudes and beliefs that may hinder effective treatment (e.g., the belief that opioid use will result in addiction). Ask about expectations and goals for pain management.

In an acute care setting, time limitations may dictate an abbreviated assessment. At a minimum, assess the effects of the pain on the patient’s sleep and daily activities, relationships with others, physical activity, and emotional well-being. In addition, include the ways in which the patient describes the pain and the strategies used to cope with and control the pain.