Pain can be defined as an unpleasant sensory or emotional experience that is associated with real or potential tissue damage. It is a complex modality that is both a symptom and a perception. It is also essential for survival. Although most sensory input is informational, pain is protective. Nociceptive (noxious) stimuli trigger behavioral processes that protect tissue from damage and are often associated with behavioral changes directed at preventing further damage. Additionally, pain perception can be influenced by past experiences and is therefore highly variable and not necessarily proportional to the extent of tissue damage.
At the cellular level, pain is described as nociceptive (Latin for nocere, “to hurt”) meaning that it is noxious or potentially damaging. Noxious stimuli activate receptors (nociceptors) that will then initiate an action potential (AP) in pain nerve fibers. The impulse is transmitted by nerve fibers into the spinal cord and eventually to the brain via ascending sensory tracts. Ultimately, the signal that began from the activation of nociceptors in the peripheral nervous system is interpreted as pain by the cerebral cortex. One caveat to the several well-documented pain pathways is the observation that the intensity of pain is not necessarily a direct function of the activation of pain receptors. Pain transmission can be modulated such that endogenous analgesia is produced resulting in a perception of decreased pain intensity. Conversely, pain can also be exaggerated or perceived as originating from a different source. The endogenous analgesia mechanism was initially suggested based on anecdotal accounts by physicians treating soldiers on the battlefield, and is now the basis for modern-day pharmaceutical pain control using opioids.
Visceral: Pain caused by damage/disease involving viscera, e. g., stomach, heart, or gastrointestinal (GI) tract. Pain is described as vague, diffuse, and difficult to localize. Visceral pain can ultimately involve the body wall at which point it becomes somatic and therefore well localized.
Referred: Pain of visceral origin that appears to originate from somatic structures. There are several hypotheses proposed to explain referred pain (a). The convergence theory suggests that referred pain is due to the convergence (synapsing) of visceral and somatic afferents on the same sensory neurons in the dorsal horn of spinal cord. This mechanism involves sensory information from both visceral and somatic structures entering the spinal cord at approximately the same level. Typically, visceral and somatic afferents synapse on specific/separate second-order neurons. There are circumstances where collaterals from visceral afferents will synapse on somatic second-order neurons. If visceral afferents synapse on a somatic second-order sensory neuron, which typically receives somatic information, the visceral sensory information is ultimately interpreted as somatic (b). A second hypothesis, the common dermatome principle, states that referred pain originating from a structure can refer to a different structure that developed from the same dermatome (c). Both hypotheses can explain angina (cardiac pain) localizing to the left shoulder/arm ().
Neuropathic: Pain resulting from abnormal signaling due to injury or dysfunction of peripheral nociceptive neurons. The deficit may involve peripheral nerves or central nervous system (CNS) pathways. Pain is often poorly localized. This disorder can be caused by compression, transection, ischemia, and infiltration. Neuropathic pain can be acute or chronic and intractable.
Phantom limb: Painful sensations experienced after amputation of extremities. Reported to be as high as 70% among amputees in the first week post surgery. Pain is typically intermittent and described as shooting, stabbing, throbbing, and burning and may subside over time. The etiology of this disorder is unclear. The “pain” is thought to be originating from the CNS and the cause is proposed as somatosensory “memory” or central sensitization. Other factors believed to be involved in the phenomena are: the formation of scar tissue at the site of amputation, development of neuromas, and damaged nerve endings. Treatment is often unsuccessful.
Peripheral neuropathy: A degeneration of distal nerves common in several diseases. Pain is described as burning, often involving the toes and feet. Diabetes mellitus is one of the most common causes of peripheral neuropathy.
Central pain syndrome: This disorder is due to injury to central pain pathways that include sensory pathways in the spinal cord and the thalamus. Common sources of lesions include: infarction, hemorrhage, abscesses, tumors, and trauma. The intensity of the pain ranges from mild to excruciating. The pain is often constant and significantly impacts the patient’s quality of life. The mechanisms involved in central pain syndrome are poorly understood at this time. Treatment is not universally effective and typically does not eliminate pain.
(b) Convergence theory of referred pain. Nociceptive (and non-nociceptive information) can converge on the same second-order neuron from different parts of the body. (c) The common dermatome hypothesis states that pain from a structure can “refer” to a different structure that developed from the same dermatome.
These pain receptors transduce stimuli into receptor potentials that in turn initiate afferent AP (see Chapter 4).
Sensory neurons (pseudounipolar) have a single axon and a central (CP) and peripheral (PP) axonal process (see Chapter 3).
Nociceptors are also called free nerve endings (see Chapter 11).
There are four neural processes involved in the physiology of pain: transduction, transmission, modulation, and perception. The situations that may result in the initiation of these processes may include:
Transduction involves the activation of nociceptors in peripheral tissues. Chemical mediators released in response to tissue damage modulate free nerve endings resulting in activation. These molecules sensitize the receptors and facilitate the conversion of the stimulus into an AP.
Generation of an AP and subsequent pain impulse require an exchange of sodium and potassium ions (polarization and repolarization) in the nerve cell membrane (see Chapter 4).
The central process of the sensory neuron enters the dorsal horn of the spinal cord and synapses on second-order cell bodies located in Rexed lamina (RL) I (see Chapter 10). Fibers from the second-order neurons cross and ascend in the spinal cord. These fibers combine to form the neospinothalamic tract, which also constitutes the lateral spinothalamic tract (LST). The LST projects to the thalamus.
A number of both ad and C fibers synapse on cell bodies located in RL II (substantia gelatinosa) and then project to second-order neurons located in RL IV–VI (nucleus proprius). Most of these axons cross and ascend in the anterior region of the spinal cord and are thus called the anterior spinothalamic tract (AST). The AST is part of the paleospinothalamic tract which also projects to the thalamus. Additionally, the paleospinothalamic tract includes nerve fibers that project to other structures and are known as the spinorecticular tract, the spinomesencephalic tract, and the spinotectal tract (tectum).
The oldest of the ascending pain pathways is the archispinothalamic tract. In this pathway, the first-order sensory neurons synapse in RL II (SG) and ascend to laminae IV–VII. From these RL, the fibers ascend and descend to ultimately make their way to the medullary reticular formation-periaqueductal gray (MRF-PAG) area. Some fibers will continue toward the thalamus and send collaterals to the hypothalamus and limbic nuclei.
Both anecdotal and experimental observations support the concept of endogenous pain modulatory mechanisms. Although it has been shown that there are several modulatory pathways, three major regulatory mechanisms play a significant role in the inhibition of pain in humans: segmental inhibition, endogenous opioid system, and descending inhibitory tracts (see Section 14.5).
It is commonly accepted that there are differences between the reality of a painful stimulus and the individuals’ response to it. Pain perception involves much more than just the neural impulse. This phenomenon reflects the complex neural loops involved in pain transmission as well as the recognition that there is a demonstrable psychological component to pain. Emotional aspects of pain are most apparent in individuals experiencing chronic pain but are also important in the treatment of acute pain.
The emotional response to pain involves cortical and subcortical structures that include the limbic system, the anterior cingulate gyrus, and part of the prefrontal cortex. Studies have shown that in cancer patients a frontal lobotomy can completely block the affective aspects of pain. These patients can recognize and feel pain but report that it doesn’t “bother” them.
Attention: Focusing attention on pain makes the pain worse. Distracting patients is highly effective in reducing pain. Burn patients report excruciating pain during therapy even opioids are given, however, if distracted with video or virtual reality, they report a fraction of the pain.
Expectations: Patients’ expectations of how much pain they should feel can influence how much pain they feel and their response to treatment. Cultural influences can also influence expectations and thus pain perception. The placebo effect is also influenced by the patients’ expectations.
Beliefs and coping: Psychosocial issues such as coping skills, tendency to “catastrophize,” self-efficacy, and what patients “believe” about their pain can impact how much pain they feel and how it affects them.