Nociception and Pain

Review the physiology of nociception and forms of stimulus energy that activate them

Nociception (excitation of sensory neurons by potentially damaging stimuli) is caused by activation of nociceptors, which can be activated by mechanical, thermal, and/or chemical energy. Nociceptors are found in the skin and also in deep tissues, and respond to different stimuli (some respond to only one type of stimulus, while others are polymodal- that is, they respond to multiple types of stimuli). Nociceptors that respond to mechanical stimuli tend to have relatively high thresholds compared to the other types of nociceptors.

Define the difference between nociception and pain

Nociception, as I just mentioned, is the excitation of sensory neurons by potentially damaging stimuli. Pain is a subjective perception, which may or may not occur in the presence of nociception as it can be modulated independently.

Explain the physiological basis of fast and slow pain and central pain pathways

"Fast sharp" pain and "slow dull" pain are caused by different nerve fibres. "Fast sharp" pain is caused by Aδ fibres, which are myelinated (and therefore fast) and have small receptive fields. "Slow dull" pain is caused by C fibres, which are unmyelinated and have larger receptive fields.

I didn't quite understand the central pain pathways (neuroscience is not my forte), but to my understanding, the pathway that has been studied the most is the spinothalamic pathway. Sensory nerves cross over in the spinal cord and travel to the thalamus, and then to the primary somatosensory cortex, association cortex, and so on. There are also projections to the reticular formation and central lateral thalamus, which are responsible for arousal and autonomic responses, and projections to the insula and cingulate cortex, which are responsible for emotional responses.

Another important point to touch on is the concept of "referred pain"- the idea that we might get pain in an area other than the affected area (e.g. pain in the left arm during a heart attack). "Referred pain" might be due to convergent wiring- sensory nerves from the skin and the affected organ synapse onto the same interneuron in the spine, and the brain can't figure out where the signal originated from, so you perceive the pain as coming from all of the regions that send signals to that interneuron.

Describe the mechanisms of hyperalgesia and allodynia

Hyperalgesia is increased intensity of pain from normally painful stimuli, whereas allodynia is pain from normally non-painful stimuli. Hyperalgesia and allodynia may be due to peripheral tissue damage, lesions to dorsal roots or alterations in the excitability of central circuits.

First, let's look at peripheral tissue damage. When tissue is damaged, it releases a whole bunch of stuff, like potassium, bradykinin, serotonin, and prostaglandins. All of these substances can increase the excitability of nociceptors. Nociceptors can also release substance P, which stimulates histamine release from mast cells, which also increases the sensitivity of nociceptors. Therefore, peripheral tissue damage can cause hyperalgesia. Even surrounding undamaged tissue can experience hyperalgesia.

I don't really have any examples of lesions to dorsal roots, but I do have an example for an alteration in the central circuit. Lesions to the thalamus can cause thalamic pain syndrome, which is chronic severe pain caused by lesions to the thalamus. Other kinds of pain that occur in the absence of nociception include phantom limb pain, and possibly also migraines.

Explain some mechanisms of modulation of pain and pain relief including intrinsic analgesic pathways

As well as nociceptive fibres, we also have non-nociceptive afferents, such as Aα and Aβ fibres. Non-nociceptive fibres can activate inhibitory interneurons, reducing the transmission of pain signals. Aα and Aβ fibres can be activated by rubbing the skin.

Descending "analgesic pathways" can also help modulate pain. These pathways mainly use norepinephrine and serotonin, and can act via two main pathways. Firstly, they can directly inhibit transmission of nociception (just like Aα and Aβ fibres), or they can indirectly inhibit it via enkephalin-releasing interneurons. Enkephalin binds to opiate receptors, and can influence the amount of Ca²⁺ uptake (and therefore neurotransmitter release) in presynaptic nociceptive neurons, as well as hyperpolarise post-synaptic neurons. Opiates relieve pain by activating the same pathway. (See here for more information on analgesic drugs.)