Week 3 Flashcards
Pain
A protective sense
“An unpleasant sensory and emotional experience associated with actual or potential tissue damage”
A combination of sensory (discriminative) and affective (emotional) components
Pain is always subjective
Nociception- the sensory component of pain alone
The nociceptor, peripheral ‘perception’ of pain
Free nerve endings in skin, muscle, viscera pick up stimuli
High threshold receptors
Activated by intense (noxious) stimuli; sufficient to cause tissue damage
Action potential firing rate proportional to stimulus
Generates action potential
-stimulus intensity encoded through firing rate
Pain generating stimuli: injury, heat, cold, inflammation, pH
Two kinds of nociceptor
Mechanical nociceptor:
-activated by strong shearing force in skin
-eg cut, strong blow
-sharp pain
-Adelta fibres
Polymodal nociceptor
-respond to many stimuli
-eg sharp blow, damaging heat (>46C), chemicals released by damaged tissue
-(K+, H+, histamine, prostaglandins, bradykinin)
-dull burning pain
-C fibres
Primary afferent fibres all excitatory
Noxious information carried by primary afferents
Fast transmission- sharp pain, myelinated Adelta
Slower transmission- dull, burning pain, C fibres
Primary afferent fibres entry into the CNS
First order neurone synapses with second order neurone in the substantia gelatinosa, lamina II
Nociceptive inputs to the dorsal horn
Laminar organisation
Synapse with second order neurons
Ab: III-V
Adelta, C: cutaneous I-II (topographic), viscera I,V,X (diffuse)
Directly or indirectly (via interneurons) make contact with projection neurons
Substantia gelatinosa= lamina II
The dorsal horn- a gateway to pain
Local interneurons make up a vast majority of dorsal horn neurons
Inhibitory make sure neurons don’t send output-> otherwise would feel pain often
Modulate activity of projection neurons
Majority inhibitory
-spontaneously active, or stimulated by primary afferent input
-pain signal must overcome inhibition to be sent to brain
GATE THEORY OF PAIN
gate theory of pain (Wall and Melzack, 1965)
Gate closed to non-noxious input:
-Ab mechanoreceptor fibres excites 3rd neurone but also excites inhibitory interneurone because dont want the non noxious stimuli to be sent to the brain as a pain signal
Arrival of a noxious stimulus:
-Adelta/C fibres: excites 3rd neurone, and excites another inhibitory interneuron which then inhibits the gatekeeper interneurone so no longer inhibitory and pain signals are sent to the brain, responds to stimulus
Closing the gate to prevent pain signal:
-increase input of non noxious stimuli AB fibres which will increase excitation of gatekeeper interneurone to inhibit pain stimulus ascending signal
Clinical significance of the gate control theory
Increased non noxious afferent input to spinal cord for analgesic effect
Transcutaneous electrical nerve stimulation (TENS)
-electrical current in skin activate AB fibres relieve pain, increase gatekeeper neurone
Physical therapies
Acupuncture
Ascending spinothalamic pathway
Perceived at subcortical level
Localised- cortical level
Limbic system- affective component
Enters dorsal horn synapses decussates in spinal cord, ascends to thalamus synapses 3rd order neuron ascends to cortex
Descending pathways: feedback control
Brain stem nuclei (rich in opioids)
Release of 5-HT, noradrenaline, enkephalin (endogenous opioid)
Closing the spinal gate, intrinsic analgesia system
Prevents ascending pain signals
Synapses and inhibits in the dorsal horn to the ascending pain fibres
Decussates in subcortical region of brain synapses in thalamus and then descends
Facilitated pain
Normal physiological pain
Sensation of pain= afferent input
Duration and intensity
Persistent/chronic pain states increases sensitivity to pain
Process of peripheral and central sensitisation
Modification of neurotransmission
Plasticity
Changes in pain sensation induced by injury
Hyperalgesia: enhanced painful response to a normally painful stimulus
Allodynia: painful response to a normally non-painful stimulus
If repeated more sensitive to pain, pain threshold moved
Peripheral sensitisation and primary hyperalgesia- neurogenic inflammation
Sensitisation of polymodal nociceptor more sensitive response to a smaller stimulus
Noxious stimulation activates nociceptor directly and causes release of various factors in damaged skin/underlying tissue
Antidromic action potential propagation can occur along of primary afferent fibre branches that innervate injured tissue
This stimulates substance P and CGRP release from peripheral nerve ending that acts on the vasculature to cause plasma extravasation and immune cell migration into tissue.
Immune cells release proinflammatory substances (prostaglandins, H+, bradykinin, NGF, cytokines) that act on nociceptor to lower threshold for AP generation
Lower threshold= sensitisation
Antidromic action potential propagation along fibre branches that innervate injured and neighbouring uninjured tissue, result in sensitisation of neurons that also innervate the neighbouring uninjured tissue. This depends on the overlap of sensory territories- contributes to secondary hyperalgesia
Peripheral sensitisation
Primary hyperalgesia: increase pain sensitivity that occurs directly in the damaged tissue
Throbbing: pulsatile movement in blood vessels in a sensitised neurones respond to pulsatile movement generating pain normally wouldn’t respond- allodynia
Peripheral sensitisation promotes central sensitisation
Secondary hyperalgesia: increased pain sensitivity distant from the site of injury
Signalling acute pain
Primary afferent AP, release glutamate not substance P, glutamate acts on the AMPA receptor sufficient to cause second AP by 2nd order neurone
Incoming Adelta/C fibre pain signal 2AP—high fidelity—> ascending pain signal 2 AP
Input=output
