Neurobiology of pain Flashcards
Mention three chemicals that cause pain and describe their pathways.
Serotonin (5-HT)-
5HT2A receptor is linked to TRPA1 or TRPV1 which cause an increase in pain feeling.
Prostaglandins-
In response to inflammation arachidonic acid is released from the membrane phospholipids by phospholipase A2. Arachidonic acid is converted to prostaglandin E2 via cyclooxygenase-1/2 (COX1/2). Prostaglandin E2 binds to EP1-4, all involved in sensitization of nociceptors.
Bradykinin -
when the tissue is injured, negatively charged substances such as collagen are exposed. Collagen and other negative substances will activate factor VIII, a protease that plays a role in the blood-clotting cascade, which in turn will activate the inactivated enzyme kallikrein. Kallikrein will cleave kininogen into two different products (Bradykinin + kallidin) which are both involved in inflammation and pain sensation.
Describe 3 different nociceptive spinal tracts. +
Spinothalamic tract-
The spinothalamic tract is split into two sub sections:
The paleospinothalamic tract- this tract carries information important to the autonomic and emotional aspects of pain.
The neospinothalamic tract, this tract carries information important for the localizing and discriminative aspects of pain. These neurons have very small receptive fields to aid with their function.
Spinoreticular tract-
Wide receptive fields.
Suggested to be involved in general aspects of pain such as pain onset.
Involved in the autonomic response to pain.
Spinomesencephalic tract-
Involved with the affective and emotional component of pain.
PAG seems to be involved in the endogenous analgesic system of the brain.
Explain the gating theory and how it is involved in pain modulation.
The gating theory proposes that the activation of the cutaneous touch fibers has an inhibitory effect on the presynaptic nociceptive neurone blocking the transmission to the spinal nerve in the dorsal horn, thereby preventing the noxious stimulus to reach the higher brain regions. Therefore, the gate is closed for the nociceptive stimulus. Another mechanism which can affect the nociceptive afferents at the spinal level includes the descending analgesia pathway which can act on the presynaptic neurone, blocking its transmission.
label the diagram
A – Periaqueductal gray B – Locus Coeruleus C – Nucleus Raphe Magnus D – Serotonergic neurone E – Nor-adrenergic neurone
Describe the interactions of morphine in producing analgesia
Morphine produces analgesia is by the inhibition of glutamate release from primary afferent neurons, preventing the transmission of pain signals at this level. Morphine also acts to increase the excitatory effect in the periaqueductal grey by inhibiting GABA, thus preventing the inhibition of the periaqueductal grey, increasing periaqueductal activity, and so increasing analgesic activity.
Contrast and compare the endocannabinoid receptors, CB1 and CB2
CB1 receptors are highly expressed in the central nervous system, and are concentrated in the axon terminals of inhibitory neurones and excitatory projection neurones. In contrast, CB2 receptors have a low expression in the central nervous system, but are highly expressed in cells of hematopoietic (blood stem cell) origin. However, both receptors show an increase in expression following a noxious stimulus, such as nerve damage or inflammation, and are involved in nociception.
Describe “endocannabinoids” with reference to their role in pain perception, and name and describe the receptor efficacies of two common endocannabinoids
Endocannabinoids are arachidonic acid derivatives that activate cannabinoid receptors to suppress sensitisation and neurogenic inflammation, recruited to regulate pain signals and reduce perception of pain. Anandamide (AEA) and 2-AG are the two best characterised endocannabinoids. 2-AG is a high efficacy agonist for CB1 and CB2 receptors, whilst Anandamide is a low efficacy agonist for CB1 receptors, and shows even lower efficacy for CB2 receptors.
Name at least four key brain regions involved in placebo analgesia and the three neurotransmitter systems they utilize.
The key brain regions in placebo analgesia are: rostral anterior cingulate cortex (rACC), oribitofrontal cortex (OFC), nucleus accumbens (NAc), prefrontal cortex (PFC), insula, amygdala, periaqueductal gray (PAG), thalamus. The neurotransmitter system they utilize are opioid, dopaminergic and endocannabinoid.
Describe the role of endocannabinoids in placebo analgesia.
Endocannabinoid placebo analgesia occurs following anti-inflammatory drug conditioning. It is independent of the opioid system and exerts its effects via the CB1 endocannabinoid receptors. This system affects both the analgesia and reward reinforcement aspects of the placebo treatment.
