The Pathophysiology of Pain

What Is Pain?

From a clinical perspective, pain is far more than a distinct type of physical sensation. The International Association for the Study of Pain provides a practical definition of pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”¹

Types of Pain

Transient, or nociceptive, pain results from a noxious stimulus, such as injury, disease, or inflammation. Such pain may, but does not always, require medical attention.¹

Neuropathic pain is caused by damage to the brain, spinal cord, or peripheral nerves.¹

Acute pain results from local tissue damage and generally subsides within weeks.²

Chronic pain extends beyond the period of healing and disrupts both sleep and normal activities of living.¹

Disease-specific pain is typically caused by a chronic disease such as osteoarthritis or fibromyalgia.¹

The Role of Pain

Both transient and acute pain have an apparent survival benefit. Rapidly pulling away from a burning object, for example, helps protect the body. Behaviors such as resting and immobilizing an injured extremity, such as a sprained ankle, may help promote natural healing and the restoration of normal function.³ In contrast, chronic pain states have no clear protective or restorative value. Consequently, chronic pain is often considered indicative of sustained pathophysiology, provoked by inflammation or nerve injury.³

The Neurobiology of Pain

The neurophysiologic underpinnings of pain can be divided into 4 stages: transduction, transmission, pain modulation, and perception.¹ At every point in the process, the intensity and propagation of pain signals can be either inhibited or facilitated by neural pathways originating in the brain. This capacity to modulate signaling may account, in part, for wide variations in pain perception between different individuals who sustain the same injury.¹

Transduction occurs when a stimulus, such as pressure, thermal energy, or chemical irritation, is converted into a nerve signal (eg, an action potential). This occurs at the ends of sensory nerve cells whose terminals are sensitive to this type of activation.¹ These cells, known as nociceptors, are distributed throughout the body.³

Transmission is the process of transferring pain information from the peripheral to the central nervous system.¹ Signals are transmitted along the axons of nociceptors. These small-diameter nerve fibers comprise 2 main types: unmyelinated C-fibers, which conduct impulses slowly (~0.5–2 m/sec), and thinly myelinated A-delta fibers, which carry impulses at a faster rate (~5–30 m/sec).^1,2 Most primary sensory nerve fibers, including nociceptors, synapse with second-order neurons in the dorsal horn of the spinal cord. From here, projection neurons carry information to the brainstem, thalamus, and hypothalamus, as well as to reflex arcs to mediate an avoidance response.²

Pain modulation refers to the transmission of pain signals through the dorsal horn.¹ Many of these signals never reach consciousness because they are dampened by intrinsic modulatory activity within the central nervous system.² The gate control theory advanced by Melzack and Wall in 1965 focused on descending pathways from the brain to the spinal cord that inhibited pain signaling.⁴ The current view is that signals originating in the brain can both inhibit and facilitate pain signal transmission.³ Neurotransmitters involved in these pathways include endogenous opiates (enkephalins, dynorphins, beta-endorphins),² serotonin, and norepinephrine.

Perception of pain is the awareness—typically an uncomfortable awareness—associated with a specific area of the body. It depends on the transmission of pain signals through the thalamus to the cortex and limbic system.¹ At this point in pain processing, perception of the pain experience is influenced by social and environmental cues, as well as by cultural conditioning and past personal experiences.¹

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