Substance P: An Introduction
The reason I decided to put Substance P separately, despite the fact that this neurotransmitter is actually a peptide in composition, as seen by the picture above, is that Substance P plays a role in our sense of pain perception and also within the inflammatory process via its own pathway. The pain pathway, when it is working correctly, is a source of protection for the body as it encourages us to keep the damaged area still whilst it heals and also gives us the opportunity to learn over our lifetimes what things are dangerous (and therefore need to be avoided wherever possible) and what things are safe. However, it does not always work correctly: pain is protective when it is acute (short in duration), but damaging in more ways than one when it chronic or long in duration (usually more than a few weeks at most from broken limbs).
The pain pathway has three specialized types of receptors that detect different signals: these receptors are commonly referred to as nociceptors. These receptors detect mechanical damage, temperature extremes and other harmful stimuli such as chemical release, and are called mechanical nociceptors, thermal nociceptors and polymodal nociceptors, respectively. The type of pain that these receptors send to the brain are quite different. Both mechanical and thermal nociceptors are responsible for generating ‘fast pain’, whereas the polymodal nociceptors are responsible for generating ‘slow pain.’ The characteristics of pain are demonstrated in the table above.
There are multiple parts of the nervous system (particularly within the brain) involved in
processing painful sensations.
Step 1: Painful Stimuli
The pathway begins when a painful stimuli occurs either inside or outside of the body, such as your finger getting burned or crushed in the hinge of the door: they would activate the thermal and mechanical nociceptors, respectively.
Step 2: Message to Spinal Cord
The activation of the nociceptors triggers signals along afferent pathways. Afferent pathways are pathways that travel from the extremities toward the spinal cord. Substance P is then released at their axon terminals within the dorsal horn of the spinal cord.
Step 3: Activation of Ascending Pain Pathways
From the spinal cord, the pain pathway then travels towards the brain and splits off into two different directions. Some of the signal goes to the reticular formation within the brain stem and increase your conscious alertness to the pain signal, and the other parts of the signal end up at the thalamus, which increases your perception of the pain signal.
Step 4: Localisation of Pain
Some of the pain signals that ended up at the thalamus then travel up to the somatosensory (sense of touch) cortex, which helps to localize the source of the pain. The ability of the somatosensory cortex to localize the pain source is dependent on the type of pain: fast pain is easily localised, but slow pain cannot be localized easily.
Step 5: Behavioural and Emotional Response to Pain
Other parts of the pain signal at the thalamus then cross over the hypothalamus and limbic system. Subsequently, the pain signals at the reticular formation then travel upwards from the brainstem and end up at the same destination. At the hypothalamus and limbic system, behavioural and emotional responses to pain are triggered: you may curse at the top of your voice, get angry or cry as a response to the pain in your body.
Role of Opiates in the Pain Pathway
Opiates were previously discussed in NTs: Peptides. These are the brain’s natural painkillers, and they block the pain signal by originating within the periaqueductal grey matter (the matter located outside of the midbrain) to the reticular formation in the brainstem and then to the relevant nociceptor. Endogenous opiates are released and lock into opiate receptors, which prevent the release of substance P, therefore preventing the perception of pain (even if the stimuli is continuous) by stopping the transmission of pain signals to the dorsal horn of the spinal cord.