The pain pathway starts with nerve endings that respond to noxious stimuli (heat, chemical or mechanical stimuli). These are called nociceptors. They are broken into:
Unmyelinated C fibres. These have a high stimuli threshold and produce slower burning pain.
Myelinated A-δ fibres. These have a low stimuli threshold and result in acute pain perception.
The actual configuration is a little more complex with a number of different types of C & A fibres that respond to differing types of stimuli (heat, cold, acid etc).
Once an action potential is stimulated this passes up the nerve fibre (First order neuron) to the dorsal horn of the spinal canal. Connections (synapses) are made with secondary afferent fibres (Second order neurons). These cross over the spinal cord and travel up to the contralateral half of the brain.
There are a number of spinal tracts that transmit signals to different areas of the brain (Spinothalamic, Spinocervicothalamic (absent in humans), Spinoreticular & Spinocerebellar Tracts). In the Thalamus, the 2nd order neurons synapse with Third order neurons which travel to areas of the cortex. The spinothalamic tract is associated with pain localisation while the spinoreticular tract is associated with the emotional aspects of pain.
Pain response can be modulated at a number of levels. Interneurons from A – β fibres (stimulated by non-noxious stimuli such as rubbing) connect with the afferent nerve fibres in the dorsal root ganglion of the spinal cord and suppress pain (why we benefit from rubbing the sore spot). Descending tracts from the midbrain and medulla connect with the dorsal horn of the spine and suppress the pain response. These areas contain opioid receptors (responsive to exogenous & endogenous opioids).
Pain can be modulated at different levels. NSAIDs act to regulate COX 2 activity which regulates prostaglandin production which affect the sensitisation of nociceptors. Opioids act on the brains opioid receptors which modulate the dorsal horn ganglia activity. Local anaesthetic agents act directly on the afferent nerve fibres by blocking the ion channels that allow sodium transfer in & out of the nerve fibre (creating an action potential).
Normal pain responses can change. Hyperalgesia is the increased sensitisation to pain either at the nociceptor level, or within the spinal cord. In this situation the reaction to a painful stimuli is greater than expected. The signal to the brain is either enhanced at the nociceptor or spinal cord level. Allodyne is a painful response to non-noxious stimuli (such as brushing your arm). It is believed to be initiated through A-β fibres (these respond to non- noxious stimuli) that manage to link with 2nd order neurones in the spinal cord that normally respond to nociceptors associated with pain resulting in exaggerated painful responses to non-noxious stimuli.
The importance of understanding pain pathways centres on our ability to regulate a patient’s pain perception. We are taught about ‘pain windup’ where one stimuli ads on top of another making it much more difficult to control & reduce the patient’s pain response. By understanding the various steps of the pain pathway it is possible to plan patient pain management when they experience painful noxious stimuli such as surgery. This is an exciting field and is likely to see new and safer advances in the way pain is controlled. Monoclonal antibody development specific to certain nociceptor receptor sites offers the opportunity of pain management without the side effects of many of our current pain medications.