Pain Defining pain an unpleasant and emotional experience associated with actual or potential tissue damage A combination of sensory

(discriminative) and affective (emotional) components Pain = subjective

Nociception The sensory component of pain Free nerve endings in skin, mucscle and viscera Activated by intense (noxious) stimuli Generates AP o Stimulus intensity encoded through firing rate o Propagated centrally Mechanical nociception fibres o Activated by strong shearing forces in the skin feel sharp pain o E.g. cut or strong blow Polymodal nociceptor dull burning pain c fibres o May respond to many stimuli e.g. sharp blow, damaging heat > 46 oC o Chemicals released by damaged tissue  K+, H+, histamine, PGs, bradykinin 1o afferent fibres are all excitatory

Noxious information carried by primary afferents Fast transmission = A sharp pain

Slow transmission = C fibres = dull, burning pain

Nociceptive inputs to the dorsal horn Laminar organisation

Somatotropic organisation Synapse with second order neurones directly or indirectly (via interneurons)

NB substantia gelatinosa = lamina II

Dorsal horn Local interneurons make up the vast majority of dorsal horn neurones Modulate activity of projection neurones Majority inhibitory o Spontaneously active or stimulated by primary afferent input Pain signal must overcome inhibition to be sent to the brain o = gate theory of pain

Gate theory of pain does not equal pain until it reaches the brain Substantia gelatinosa (inhibitory interneurone) lamina V (ascending pain signal) brain

Gate closed to noxious input

5-HT, noradrenaline, enkephalin Close the spinal gate (intrinsic analgesia system) Encephalin = endogenous opioid

Facilitated pain Normal physiological pain o Sensation of pain = afferent input o Duration and intensity Persistent/ chronic pain states - sensitivity to pain Process of peripheral and central sensitisation o Modification of neurotransmitter o Plasticity

Changes in pain sensation sensed by injury Hyperalgesia enhanced painful response to a normally painful stimulus Allodynia: painful response to a normally non-painful stimulus

Mechanisms underlying heightened pain Sensation of peripheral nociceptors

Neurogenic inflammatory soup

threshold for response signal with less stimulus

Primary Hyperalgesia pain sensitivity that occurs directly in the damaged tissue Peripheral sensitisation promotes central sensitisation Increased primary afferent input alters the responsiveness of spinal output neurones

Secondary Hyperalgesia Increased pain sensitivity distant from the site of injury E.g. when touching around bruise

Signalling acute pain

High frequency input caused by peripheral mechanical nociceptors Preferential substance P release Allows NMDA receptor activation Ca2+ 2o messenger cascades

Summary Nociceptors o Peripheral nerve endings of primary sensory neurones o Activated by intense (noxious stimuli) o Mechanical A and polymodal C fibre nociceptors Gate control theory of pain o Inhibitory control in spinal dorsal column Spinothalamic tract transfers ascending signals to the brain o Pain experienced in higher CNS o Descending control from brain stem Mechanisms underlying heightened pain sensation o Peripheral sensitisation primary Hyperalgesia o Central sensitisation - secondary Hyperalgesia