Pricks, pangs and paroxysms: the pathways of pain perception.

A Project Encephalon & The Science Paradox Collaboration article



Abstract


One of the most important forms of sensory perception, the one responsible for an organism's survival, is pain. Pain is not a one-dimensional experience, it is nuanced and complex, both in the ways in which it is transmitted through our body and in the manner that we perceive it. What is the neuroanatomy of pain perception? Over millennia, several pathways have evolved for its signals to travel through our body, which are a combination of different kinds of sensory fibres, neurotransmitters, and locations that these signals are relayed to. These differences in structure and function enhance our perception of pain and enable us to assess its location and severity. In this article, we will explore two of the main pain pathways, what makes them unique, and how that translates to our own experiences of pain perception.


 

As a kid, I remember a frequently asked question in exams - “What distinguishes a living being from a non-living one?” While the younger version of me would have probably answered on the lines of movement, metabolism etc, as I grew older and became familiar with the concepts of sensation, an important difference began to make sense to me - the ability to sense and react to stimuli. Almost all life forms one way or the other respond to various stimuli around them, whether it’s internal or external. We have various receptors present in our body such as mechanoreceptors, olfactory receptors etc. which connect themselves to the nervous system and the brain, which then further directs the response in the effector organs because of this stimulus. Of these, the ability to sense pain is very important as it can prevent or minimise tissue injury.


Our experience of pain occurs in two phases, first, a fast, sharp, localized sensation of it, and later, a slower, duller sensation that we aren't quite able to pinpoint to a specific area. These differences in our perception aren't merely a coincidence; they are part of a complex system of transmission that has evolved over several millennia, which helps us appreciate the most subtle differences in our environment.


Sensory neuron receptors that are responsible for transmitting pain signals are called nociceptors. Unlike other kinds of nerve fibres, they do not have specialized receptors but have free, unmyelinated nerve endings that branch out and form networks in the organs they innervate. Further, they only get activated and transmit an impulse when a noxious stimulus reaches or surpasses a certain threshold level.



There are primarily two types of fibres that transmit pain: A-delta and C-fibres. A delta fibres are myelinated and have a larger diameter than C-fibres and thus, conduct nerve impulses faster. C-fibres are unmyelinated, have a smaller diameter, therefore, have a lower conduction velocity. C-fibres respond to more than one kind of stimulus, like thermal, mechanical, or chemical, and thus, are "polymodal" in nature. In contrast, A-delta fibres only respond to one kind of stimulus.


Both these kinds of fibres achieve the same outcome, so why are their modalities different? The answer comes down to the evolutionary timeline of these pathways, which has enabled us to perceive one kind of pain sooner than the other and be able to localize certain impulses and not localize others precisely.


The pathways through which pain signals travel from the spinal cord to the brain are called spinothalamic pathways. All first-order sensory fibres, including nociceptive fibres, enter the spinal cord's dorsal (posterior) grey horn, which is composed of several laminae. Here the fibres synapse with the second-order neurons, which cross over to the other side of the spinal cord and then relay messages to the thalamus and other areas of the brain. Hence this pathway is known as the spinothalamic tract. In the brain, these fibres synapse with the third-order neuron, which relays signals to the somatosensory cortex, each point of which is correlated with a specific area of the body.


Through evolution, two primary pathways for this process have come into existence: the more primitive paleospinothalamic pathway, and the more recent neospinothalamic pathway.