How do we feel Pain?

In order to truly understand how we feel pain, we must first understand the concept of nociception.

First, let’s define a few terms:

1. Noxious Stimuli: These are stimuli that have the potential to cause tissue damage. That can be a chemical stimulus (such as exposure to an acid), a mechanical stimulus (such as a pinprick or a pinch), or a thermal stimulus (such as extreme cold or heat). Noxious stimuli have the potential to cause pain, but don’t have to. For example, if you are under anesthesia and your hand is placed in hot water. Because you are under anesthesia you will not feel pain, but the hot water is still considered a noxious stimulus.

2. Myelin: Myelin is the insulation that surrounds the axon of a neuron. Neurons transmit electrical stimuli. If a neuron is an electric wire, myelin is the plastic covering around the wire that insulates it and allows the wire to transmit current faster. The more myelinated an axon is, the faster it can transmit the information it is carrying.

3. Periphery: There are two main parts of the nervous system: the central nervous system, and the peripheral nervous system. The central nervous system (CNS) includes the brain and spinal cord. The peripheral nervous system includes all the nerves outside the brain and spinal cord, such as nerves in your arms, legs, etc. In this context, the word periphery means parts of the body that are outside the CNS, such as the back, arms, and legs.

4. Nociceptors: Nociceptors are sensory neurons that transmit information about noxious stimuli. They carry information from the periphery to the spinal cord. In the spinal cord, these nociceptors terminate at the dorsal horn of the spinal cord, where they project on second-order projection neurons, otherwise known as spinothalamic neurons. These spinothalamic neurons now carry the information about the noxious stimulus previously carried by nociceptors. They then cross the midline and make their way up to the thalamus, from which they project to a network of brain areas known as the pain matrix. Activation of the pain matrix produces the percept of pain. The pain matrix includes parts of the cortex and the limbic system. The latter controls emotions and is responsible for the unpleasantness of pain. (See Fig 2.)

Now that we defined these terms, what is nociception?

Nociception is simply the activation of nociceptors. It is the neural transmission of information about noxious stimuli from the periphery to the CNS.

Nociception does not equal pain. You can have nociception without pain. Similarly, you can have pain without nociception. Unlike nociception, pain is a percept and an experience with affective, cognitive, and physiological properties

To illustrate how you can have pain without nociception, let’s consider phantom limb pain for example. Phantom limb pain is pain in a limb that is no longer there. Since the limb is absent, nociceptors are no longer present, yet one can still experience pain in the absent limb.

Fig 1. This figure shows some of the regions in the central nervous system where information about noxious stimuli is processed. Information about noxious stimuli travels from the spinal cord to the brainstem, then to the thalamus. From the thalamus, this information projects to the different parts of the pain matrix, including parts of the cortex and limbic system.

To better understand how we respond to different kinds of noxious stimuli, we must first identify the different types of sensory neurons that influence nociception, which include nociceptors and non-nociceptors.

There are two main types of nociceptors: Aδ fibers and C fibers:

1. Aδ fibers: Aδ fibers are medium diameter myelinated nociceptors of which there are two types.

1. Type I Aδ fibers respond to mechanical stimuli and very noxious heat stimuli.

2. Type II Aδ fibers however respond to lower threshold heat stimuli.

A pinprick will activate the first type of Aδ fibers, but, touching a hot stove will activate the second type of Aδ fibers.

2. C fibers: C fibers are small nonmyelinated fibers whose receptors respond to noxious heat, mechanical and chemical stimuli. Most fibers that transmit noxious stimuli are C fibers. They also have large receptive fields, meaning that they can detect noxious stimuli over a wide area of skin. They are also implicated in many chronic pain conditions.

Both sunburn and capsaicin, the active ingredient of most spicy food, activate C fibers.

Can the same noxious stimulus, activate multiple types of nociceptors?

The short answer is yes. Let’s say you touch a hot surface; you will experience two phases of pain. The first phase of pain immediate, and easily localized. This acute phase of pain is mediated by Aδ fibers. But then there is a second more prolonged phase of pain that is hard to localize. That is mediated by C fibers.

Fig 2. This figure shows the different types of sensory neurons, and where they terminate the spinal cord.

A third type of sensory neuron:

There is a third type of sensory neuron, that is not a nociceptor but does influence nociception. Aβ fibers are large diameter, heavily myelinated nerves that carry information about innocuous or non-noxious mechanical stimuli.

Even though Aβ fibers do not transmit noxious stimuli themselves, they do inhibit their transmission. That is why if you touch a hot surface, and then shake your hand repeatedly, you feel less pain. The shaking of your hand adds innocuous stimuli carried by Aβ fibers that inhibit the transmission of the noxious heat stimulus that is carried by C fibers. Aβ fiber stimulation is also known to treat neuropathic pain, which is pain due to nerve injury.