Mechanisms of Pain and Analgesia (DONE) Flashcards
What is pain? (add notes from lecture recording)
Nociception- sensitivity to and awareness of noxious/harmful stimuli
Suffering- cerebral awareness, interpretation and anxiety of pain
Made up of affective, cognitive and sensory components
The emotional component of pain
Studies have shown that less pain is felt when a patient is distracted from pain, rather than attending to it, or when they are in a good mood rather than a bad mood
Components of pain
Sensory- perception of pain characteristics: intensity, quality, location
Affective- negative emotion: anxiety, fear, unpleasant sensation
Cognitive- interpretation of pain
Behavioural- Coping strategy used to express, avoid or control pain
Physiological- nociceptive and stress response
Pain characterisation- intensity
Pain intensity is subjective but can be measured in a variety of ways
Commonly 0-10 with 0 being no pain and 10 the worst you have ever felt
0- no pain
1-3- mild pain (nagging, annoying)
4-6- moderate pain (interferes with daily life)
7-10- severe pain (disabling, unable to perform activities of daily life)
Many other scales available e.g. disease specific, children
Pain characterisation- duration
Acute: less than 3-6 months, typically non-traumatic psychologically, defined cause, high intensity
Sub-acute/inflammatory: local inflammatory changes, intensity affected by inflammatory mediator
Chronic malignant: progressive and substantial, peripheral and central sensitisations, often cancer development
Chronic non-malignant: often neuropathic in origin, long term, unrelated to peripheral injury, pathology in pathways, harder to treat and manage
Nociceptive pain
Visceral or somatic in origin, can be deep or superficial
Presence of a potentially damaging stimulus
Transient
Withdrawal reflex e.g. post surgery
Neuropathic pain overview
Peripheral or central in origin
Results from lesions to or disease of the somatosensory nervous system
Commonly chronic rather than acute
Nerve damage, not tissue
Inflammatory pain
From tissue inflammation or hypersensitivity
Associated with tissue damage and inflammation
Promotes healing by preventing contact and movement
Consequences of neuropathic pain
Hyperalgesia- increased pain to a mildly noxious stimulus, causes central facilitation and peripheral sensitisation
Allodynia- pain to a non-noxious stimulus
Spontaneous pain- pain without stimulus
Referred pain
Upper chest/left arm- myocardial ischaemia Ice cream headache- vagus nerve General- phantom limb pain Right shoulder- liver/gallbladder Left shoulder- thoracic diaphragm/lung
Phantom pain
Pain felt by a majority of amputees (50-80%)
The sensations, including pain, often maps to other areas of the body, related to proximity in cortex
E.g. trigeminal nerve severed- map of face on hand
Pain caused because body has not lost central connection in brain when limb is amputated
Some are helped by mirror therapy- ramachandran
How do we feel pain?
Nociception- peripheral activation and release of pain mediators
Primary nociceptors, C and Ad fibres
Pain gating- dorsal horn of the spinal cord
Ascending and descending secondary fibres
Pain perception- the brain (thalamus, limbic and cortical systems)
Nociception- pain detection in the periphery
Add notes from lecture recording
Pain starts with chemicals
Direct stimulators of pain fibres e.g. bradykinin, histamine, 5-HT
Affects the sensitivity of fibres to other transmitters: prostaglandins (targets of NSAIDs), opioids, TRPV1 channel (neuropathic pain)
Pain from the nociceptor to the spinal cord
Ad fibres release glutamate (excitatory, over stimulating changes the way nerves fire, involved in learning pathway)
C fibres release substance P, neurokinin A and calcitonin gene-related peptide (activating ascending fibres)
Gate control theory- pain control at spinal cord
Inhibitory neurons in spinal cord synapse prevent pain signals from going up ascending fibres
Pain stimulus blocks anything that may inhibit signal i.e. inhibitory neurons
Rubbing skin causes more interference at synapse, blocking more pain e.g. TENS machines
Central pain pathways: descending control of pain
Dorsal horn of spinal cord sends message to brain
Amygdala, somatic sensory cortex and hypothalamus influence pain that goes back down spinal cord
Midbrain periaqueductal grey stimulates lots of systems, including Raphe nuclei (production of 5-HT)
Also affects area that produces noradrenaline
Descending pathways
Periaqueductal grey receive input from different brain areas- hypothalamus, somatosensory cortex, amygdala
Acts as gatekeeper
Consequences are that brain can influence emotional component of pain
How do we treat pain?
Nociception- use NSAIDs to reduce prostaglandin activity
Pain gating- use opiates to target receptors, afferent C fibres in dorsal horn and areas of the brain
Pain perception- use opiates, improve mood through midbrain and forebrain activity, control pain circuitry through PAG and LC
Endogenous peptides are differentially distributed
Dynorphins and enkephalins- widely distributed in CNS and found in areas which control: The perception of pain Modulation of affective behaviour Modulation of motor control Regulation of ANS Neuroendocrine function
Three types of opioid receptors
Mu receptors- targeted by met/leu encephalin, B-endorphin
Kappa receptors- targeted by dynorphins
Delta receptors- targeted by met/leu encephalin, B-endorphin
Opiate receptors mediate different effects
Most widely used analgesics act on all receptors so get all effects and side effects, do not have control of selectivity
Side effects how opioids relate to receptor distribution
Mu receptors occur in the hypothalamus, cough centre of medulla, chemo-trigger zone and respiratory centre
Limbic system: most receptors found in amygdala, probably do not exert analgesic action, may influence emotional behaviour
Peripherally: gut (motility) and cardiovascular (peripheral vasodilatation, reduced resistance, inhibition of baroreceptor reflexes)
3 types of opiates
Full mu agonist- naturally occurring e.g. morphine, codeine; synthetic e.g. diamorphine, pethidine
Partial agonists- nalorphine, pentazocine, buprenorphine, meptazinol
Antagonists- naloxone, naltrexone
