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Overview of Pain


James C. Watson

, MD, Mayo Clinic College of Medicine and Science

Reviewed/Revised Mar 2022 | Modified Sep 2022

Pain is the most common reason patients seek medical care.

Pain has sensory and emotional components and is often classified as acute or chronic. Acute pain is frequently associated with anxiety and hyperactivity of the sympathetic nervous system (eg, tachycardia, increased respiratory rate and blood pressure, diaphoresis, dilated pupils). Chronic pain does not involve sympathetic hyperactivity but may be associated with vegetative signs (eg, fatigue, loss of libido, loss of appetite) and depressed mood. People vary considerably in their tolerance for pain.

Pathophysiology of Pain

Acute pain, which usually occurs in response to tissue injury, results from activation of peripheral pain receptors and their specific A delta and C sensory nerve fibers (nociceptors).

Chronic pain Chronic Pain Chronic pain is pain that persists or recurs for > 3 months, persists > 1 month after resolution of an acute tissue injury, or accompanies a nonhealing lesion. Causes include chronic disorders... read more related to ongoing tissue injury is presumably caused by persistent activation of these fibers. However, the severity of tissue injury does not always predict the severity of chronic or acute pain. Chronic pain may also result from ongoing damage to or dysfunction of the peripheral or central nervous system (which causes neuropathic pain Neuropathic Pain Neuropathic pain results from damage to or dysfunction of the peripheral or central nervous system, rather than stimulation of pain receptors. Diagnosis is suggested by pain out of proportion... read more ).

Nociceptive pain (pain caused by tissue injury) may be somatic or visceral. Somatic pain receptors are located in skin, subcutaneous tissues, fascia, other connective tissues, periosteum, endosteum, and joint capsules. Stimulation of these receptors usually produces sharp or dull localized pain, but burning is not uncommon if the skin or subcutaneous tissues are involved. Visceral pain receptors are located in most viscera and the surrounding connective tissue. Visceral pain due to obstruction of a hollow organ is poorly localized, deep, and sometimes cramping and may be referred to remote cutaneous sites. Visceral pain due to injury of organ capsules or other deep connective tissues may be more localized and sharp.

Psychologic factors modulate pain intensity to a highly variable degree. Thoughts and emotions have an important role in the perception of pain. Many patients who have chronic pain also have psychologic distress, especially depression and anxiety. Because certain syndromes characterized as psychiatric disorders (eg, some somatic symptom disorders Somatic Symptom Disorder Somatic symptom disorder is characterized by multiple persistent physical complaints that are associated with excessive and maladaptive thoughts, feelings, and behaviors related to those symptoms... read more ) are defined by self-reported pain, patients with poorly explained pain are often mischaracterized as having a psychiatric disorder and are thus deprived of appropriate care.

Pain impairs multiple cognitive domains including attention, memory, concentration, and content of thought, possibly by demanding cognitive resources.

Many pain syndromes are multifactorial. For example, chronic low back pain and most cancer pain syndromes have a prominent nociceptive component but may also involve neuropathic pain Neuropathic Pain Neuropathic pain results from damage to or dysfunction of the peripheral or central nervous system, rather than stimulation of pain receptors. Diagnosis is suggested by pain out of proportion... read more (due to nerve damage).

Pain transmission and modulation

Pain fibers enter the spinal cord at the dorsal root ganglia and synapse in the dorsal horn. From there, fibers cross to the other side and travel up the lateral columns to the thalamus and then to the cerebral cortex.

Repetitive stimulation (eg, from a prolonged painful condition) can sensitize neurons in the dorsal horn of the spinal cord so that a lesser peripheral stimulus causes pain (wind-up phenomenon). Peripheral nerves and nerves at other levels of the central nervous system (CNS) may also be sensitized, producing long-term synaptic changes in cortical receptive fields (remodeling) that maintain exaggerated pain perception. This process of chronic afferent input causing increased sensitivity (lower thresholds) and remodeling of central nociceptive pathways and receptors is termed central sensitization. It explains why the following occur:

  • Allodynia (pain response to a nonpainful stimulus)

  • Hyperalgesia (excessive pain response to a normal pain stimulus)

Substances released when tissue is injured, including those involved in the inflammatory cascade, can sensitize peripheral nociceptors. These substances include vasoactive peptides (eg, calcitonin gene-related protein, substance P, neurokinin A) and other mediators (eg, prostaglandin E2, serotonin, bradykinin, epinephrine).

The pain signal is modulated at multiple points in both segmental and descending pathways by many neurochemical mediators, including endorphins (eg, enkephalin) and monoamines (eg, serotonin, norepinephrine). These mediators interact in poorly understood ways to increase, sustain, shorten, or reduce the perception of and response to pain. They mediate the potential benefit of CNS-active drugs (eg, opioids, antidepressants, antiseizure drugs, membrane stabilizers) that interact with specific receptors and neurochemicals in the treatment of chronic pain.

Psychologic factors are important pain modulators. They not only affect how patients speak about pain (eg, in a stoic, irritable, or complaining way) and how they behave in response to it (eg, whether they grimace), but they also generate neural output that modulates neurotransmission along pain pathways. Psychologic reaction to protracted pain interacts with other CNS factors to induce long-term changes in pain perception.

Drugs Mentioned In This Article

Drug Name Select Trade
Adrenaclick, Adrenalin, Auvi-Q, Epifrin, EpiPen, Epipen Jr , Primatene Mist, SYMJEPI, Twinject
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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