Pain and Nociceptors

We have all felt pain, and although uncomfortable, it likely provided us important information about tissue damage — damage that may have gotten worse if pain had not made us aware of the problems at hand. In response to pain we tend to “protect” the damaged tissue from further use and seek appropriate medical attention. Thus pain is a critical sensation for alerting us to problems within the body such that they can be appropriately addressed.

Pain receptors, called nociceptors, are spread throughout most of the body’s tissues, with the exception of the central nervous system. They respond to nociceptive, or noxious, stimuli that lead to our perception of pain. These receptors vary in the specific stimuli that they respond to, as well as how quickly they transmit information to the central nervous system.

You likely realize that there are many noxious stimuli. Extreme temperature, a pinch, blunt impact, cuts, intestinal gas, overuse of joints, and others can all elicit the sensation of pain. This is because all of these stimuli have the ability to either directly activate nociceptors, or cause tissue damage that leads to the release of chemical substances that will activate nociceptors. You also appreciate that the sensation of pain can change over time, where an injury may start out with stinging pain, become dull, and even revert to stinging again under certain conditions, such as when someone touches the injured area. The combination of nociceptors stimulated helps determine the characteristics of the pain that is felt. Examples of nociceptor locations and types are listed in Table below.

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The silent (sleep) nociceptors listed in the table have the unique property that they are normally unresponsive to stimulation until turned “on” by chemicals released during the inflammatory process. This is one reason why, after you have stubbed your toe, or pinched your finger, you may have thought to yourself “this is going to hurt”. You know that once the tissue inflames (swells up), throbbing pain is likely to set in as further nociceptors become activated.

Besides the noxious stimulus that activates a receptor, the type of axon (fiber) that the receptor neuron contains also contributes to how we perceive pain. In general, fibers can be divided into 2 categories, with the properties listed in table below.

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Categories of Pain

Because there are multiple types of nociceptors that can transmit information at different rates, our pain sensation is not always the same. Scientists generally recognize three different pain categories (sensations or stimulus modalities), as described in table below.

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Characteristics of Pain

Hyperalgesia and Analgesia

Notice that because chemical and silent nociceptors are activated after tissue injury has set in, our sensations of pain can change over time. An initial cut will activate mechano-nociceptors, sending the fast pain signals along A-delta fibers to the brain. After inflammation in the area has set in, the chemical and/or silent nociceptors may send information along C fibers, producing a different pain sensation. If these silent nociceptors become sensitized by the inflammatory mediators, then we might experience hyperalgesia, where tissue stretch to an injured area can be sensed as a more intense pain.

Our ability to provide analgesia (reduce or block pain) is usually directed at inhibiting the local formation of the mediators that activate chemical nociceptors (this is how aspirin and ibuprofen work), blocking the transmission of signals along peripheral pain fibers (local anesthetics), or interrupting the transmission of pain signals in the CNS (endogenous or exogenous opioids as well as general anesthesia). You may have had experience with a local anesthetic during dental work or when stitches were put in. They act by blocking the ability of nerve fibers to conduct action potentials. Local anesthetics block C fibers more easily, but in time the A-delta fibers are also blocked. This is why the dentist waits awhile after giving the local anesthetic before commencing the work that would otherwise cause pain – you want to make sure your A-delta fibers are fully blocked as well!

CNS Role in Pain

Although the focus of this section has been on the peripheral sensation and transmission of resulting action potentials, keep in mind that the processing of pain, such as pain sensation, localization and the physical and emotional responses to pain, are functions of the CNS.

Receptive Field

Although the receptors of the somesthetic senses are widely distributed throughout the body, the density of receptors varies from place to place. This often leads to corresponding changes to the sizes of the receptive field for any modality. The receptive field is the area from which a sensory receptor, and its corresponding neuron, can detect a stimulus.

Receptive field areas around a sensory receptor.

Receptive fields. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 Unitied States (

The size of a receptive field might vary from a few square millimeters to tens of square millimeters, depending on receptor type and location. With larger receptive fields, the CNS has less ability to localize stimuli or to differentiate between multiple stimuli. This can be demonstrated by a two-point discrimination test where two thin objects (such as pen tips) are touched to a person’s skin in proximity to one another. If this is done on the upper back, even objects that are a centimeter apart may be interpreted by the individual to be a single object. The same distance between objects on the lips or fingertips is easily interpreted by the CNS as separate objects. Receptor densities and the corresponding size of receptive fields are represented in the CNS as the sensory homunculus with the primary somatosensory cortex.

Sensory homunculus. The size of the body regions depicted indicate the amount of cortical area dedicated to processing sensory information from that region. For example, the hand and fingers have a large cortical area devoted to processing information sent from the high density of sensory receptors found in these structures.

Sensory homunculus. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 United States (


Individual sensory neurons that are in proximity to each other are bundled together into nerves that enter the spinal cord through its posterior root or horn. The region of the skin that each spinal nerve carries information from is called its dermatome. Because there are 31 spinal nerves, there are an equal number of dermatomes, each named for the spinal nerve to which it sends information.


Dermatomes. By Mikael Haggstrom ( Public Domain.

A dermatome map is particularly useful in the diagnosis of spinal cord injuries that interrupt spinal cord transmission. An injured person will lose sensation from all their dermatomes below the level of injury.