Nociception

The Five Senses and Beyond: The Encyclopedia of Perception - Jennifer L. Hellier 2017


Nociception

Nociception or pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. It is a conscious experience involving the interpretation of sensory input that signals a noxious event and is influenced by several factors. One model describes pain in terms of three hierarchical levels: a sensory-discriminative component (location, intensity, and quality), a motivational-affective component (depression and anxiety), and a cognitive-evaluative component (thoughts involving the cause and significance of the pain). This model highlights the reality that the perception of pain is determined by a combination of several components and is very complex to both understand and manage.

Classification of Pain

Acute pain warns an organism of a potentially harmful situation (like a burn) or a disease state (such as appendicitis). Acute pain serves a specific physiologic function and lasts a brief period of time. Unfortunately, if the acute pain is undertreated or severe, it can last longer than its biologic usefulness and may have many harmful effects. Acute pain caused by surgery, acute illness, or trauma is usually nociceptive (a signal from neurons that is usually due to damage to these cell types). The goal of treating acute pain is cure.

Chronic pain results when pain persists for months to years. This type of pain can be nociceptive, neuropathic/functional, or mixed. It is associated with cancer or noncancer etiologies that result in changes to the receptors and nerve fibers within the nervous system. Additionally, chronic pain is often associated with depression, insomnia, and other personal or social problems. The goal of treatment with chronic pain is not cure, but a return to functionality.

Pathophysiology of Nociceptive Pain

Nociceptive pain is “normal” pain resulting from the activation of nociceptive fibers and includes somatic and visceral pains. Sprains and strains produce mild forms of nociceptive pain, while the pain of arthritis is much more severe. Nociceptive pain is described as either somatic or visceral. Somatic pain presents as a throbbing and well-localized pain, while visceral pain presents localized to the organ from which it originates.

Nociceptive pain occurs as a result of the activation of the sensory system by persistent noxious stimuli, a process involving transduction, transmission, modulation, and perception. Transduction is the process by which noxious stimuli are converted to electrical signals in the nociceptors. Nociceptors have the ability to distinguish between noxious and innocuous stimuli and are activated and sensitized by mechanical, thermal, and chemical impulses. Noxious stimuli may result in the release of naturally occurring chemicals, such as bradykinins, hydrogen and potassium ions, prostaglandins, histamines, interleukins, tumor necrosis factor alfa, serotonin, and substance P. These chemicals sensitize or activate the nociceptors.

Pain transmission takes place in two different nerve fiber types: A delta and C-afferent fibers. A delta fibers are myelinated and have a large diameter. When stimulated, these fibers evoke a sharp, well-localized pain. C-fibers are unmyelinated and have a small diameter. When stimulated, the C-fibers produce a dull, aching, poorly localized pain. For the central nervous system to receive the pain, the signal travels from the affected area toward the brain. These afferent nociceptive fibers synapse in various layers of the spinal cord, specifically in the region where most neuronal cell bodies reside in the dorsal horn, the “gray matter of the spinal cord.” This, in turn, results in the release of a variety of neurotransmitters including glutamate, substance P, and aspartate. The role of substance P in pain has been widely studied and how it aids in pain transmission to the brain. Substance P is released from C-fibers in response to tissue injury or to intense stimulation of peripheral nerves.

There are three major classes of nociceptors: thermal, mechanical, and polymodal. Extreme temperatures activate thermal nociceptors, which have a small diameter and are myelinated, sending very rapid signals. Mechanical nociceptors are activated by intensive pressure applied to the skin. They are also thinly myelinated fibers that conduct signals quickly. Polymodal nociceptors are activated by high-intensity mechanical, chemical, or thermal stimuli. These nociceptors have a small diameter and are nonmyelinated, conducting signals much more slowly. The nociceptors transduce signals via specialized proteins—also known as channels—such as transient receptor potential channels or those that are activated by sodium, voltage-gated sodium channels. Depolarization of the primary afferent nerves results in production of substances that are produced by tissues, inflammatory cells, and neurons. Once depolarization occurs, transmission information continues along the axon to the spinal cord and then on to higher brain centers.

Nociceptive information is transmitted from the spinal cord to the thalamus and cerebral cortex along five ascending pathways: spinothalamic, spinoreticular, spinomesencephalic, cervicothalamic, and spinohypothalamic tracts. The spinothalamic tract is the most prominent ascending nociceptive pathway in the spinal cord. These axons project into the contralateral side of the spinal cord and terminate in the thalamus. The cerebral cortex also contributes to the processing of pain. Neurons in several regions of the cerebral cortex respond selectively to nociceptive input.

At this point, pain becomes a conscious experience that takes place in higher cortical structures. The brain may take in only a limited number of pain signals, allowing cognitive and behavioral functions to modify pain sensation. Variables including relaxation, distraction, and meditation may decrease pain by limiting the number of processed pain signals. On the other hand, depression and anxiety may worsen pain.

Pain is modulated through a number of systems, including the endogenous opiate system. This system consists of neurotransmitters including enkephalins, dynorphins, beta endorphins, and mu, delta, and kappa receptors that are found throughout the central nervous system. The poppy plant extract, opium, binds to specialized proteins within the central nervous system. Scientists have expanded on this knowledge and have developed opioids, which are a group of chemicals that bind to one or more of the three opioid receptors in the central nervous system. Endogenous opioids, like exogenous opioids, bind to opioid receptor sites and modulate the transmission of pain impulses. Other receptors, including the N-methyl-D-aspartate (NMDA) receptors found in the dorsal horn, also influence the endogenous opiate system. Blockage of NMDA receptors may increase the mureceptors’ responsiveness to opiates. In addition to this mode of modulation, the central nervous system also contains a descending system that controls pain transmission through inhibition of synaptic pain transmission at the level of the dorsal horn in the spinal cord. Neurotransmitters that play an important role in this descending system include endogenous opioids, serotonin, norepinephrine, and gamma-aminobutyric acid (GABA).

Pathophysiology of Neuropathic and Functional Pain

Neuropathic and functional pain are different from nociceptive pain in that they can become disengaged from noxious stimuli or healing and are often described in terms of chronic pain. These types of pain often present as burning, tingling, or shooting sensations. In addition, persons with chronic pain may have exaggerated painful responses to normally noxious stimuli (hyperalgesia) or painful responses to normally non-noxious stimuli (allodynia).

Neuropathic pain results from direct injury to nerves in the peripheral or central nervous system. Diabetic neuropathy and phantom limb pain are two examples of neuropathic pain. Phantom limb pain can occur after traumatic or surgical limb amputation. Functional pain syndromes include fibromyalgia, irritable bowel syndrome, tension-type headaches, and sympathetic-induced pain that results from abnormal operation of the nervous system. These types of pain syndromes are complex and can be very difficult to treat, as the pain reported is not evident by examining physical findings.

The exact mechanism of neuropathic or functional pain is complex. Overall, nerve damage or certain disease states may signal changes in inflammatory pain, ectopic excitability, enhanced sensory transmission, nerve structure reorganization, and loss of modulatory pain inhibition. Pain circuits eventually rewire themselves both anatomically and chemically, producing a mismatch between pain stimulation and inhibition. This results in an increase in the discharge of dorsal horn neurons. These changes over time help explain why this type of pain often manifests long after the actual nerve-related injury or when no actual injury is identified.

Pain Management

Successful pain management depends on a comprehensive assessment of the patient including the nature of the pain and how it is impacting the patient’s life. Often, numeric rating scales are used to measure pain. Zero on the scale indicates no pain and 10 indicates the most unbearable pain. Patients should be asked frequently throughout the treatment to rate their pain in order to understand whether they are improving.

There are several classes of agents that can be used for the management of pain. These include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, anticonvulsants, and antidepressants, among others. Acute and chronic pain states are managed differently. Traditionally, acute pain is managed based on pain scores. A mild pain (score 1—3) is usually treated with a nonopioid medication like acetaminophen (Tylenol) or ibuprofen (Advil). Moderate pain (score 4—6) is treated with an immediate-release, short-acting opioid in addition to a nonopioid if needed. Severe pain (score 7—10) is usually managed with two therapy modalities, including a short-acting opioid that is rapidly titrated in addition to a nonopioid or long-acting opioid.

Danielle Stutzman

See also: Congenital Insensitivity to Pain; Nociceptors; Phantom Pain; Sensory Receptors

Further Reading

MedlinePlus. (2013). Pain. U.S. National Library of Medicine. Retrieved from http://www.nlm.nih.gov/medlineplus/pain.html

National Institute of Neurological Disorders and Stroke (NINDS). (2012). NINDS chronic pain information page. Retrieved from http://www.ninds.nih.gov/disorders/chronic_pain/chronic_pain.htm