Neurophysiology - Pain Flashcards
Define pain
Unpleasant sensory and emotional experience associated with actual or potential tissue damage
Define nociception and differentiate nociception from pain
Nociception is the process by which noxious stimuli are encoded as action potentials and transmitted from the peripheries to the CNS
Pain results from the brains interpretation of these nociceptive signals resulting in the perception of unpleasant sensory and emotional experience
Differentiate chronic from acute pain
Acute pain < 12 weeks
Chronic pain > 12 weeks
Pain that extends beyond the expected period of healing following tissue injury
Classify pain
Nociceptive (stimulation nociceptors)
- Superficial - skin
- Deep - muscle/tendon
- Visceral
Neuropathic (direct nerve injury)
What is a nociceptor
Free, unmyelinated nerve ending that generates action potentials in response to a variety of stimuli:
- K+ (damaged cells)
- Histamine (mast cells)
- Bradykinin (inflam)
- Leukotrienes (inflam)
- Serotonin (released by platelets in response to vasc. injury)
What nerve fibres carry pain sensation
A delta fibres - mechanical, thermal
- -> Relatively large diameter
- -> Myelinated
- -> 20 m/s (therefore 1st sensation of pain)
- -> Sharp and localized
C fibres - mechanical, thermal and chemical
- -> Relatively small diameter
- -> Unmyelinated
- -> 2 m/s
- -> dull and poorly localized
Describe the pathways by which pain signals are relayed to the brain
PERIPHERIES
Nociceptor –> 1st order neuron (Ad of C) –> DORSAL HORN SPINAL CORD: substantia gelatinosa (Rexed laminae II) or nucleus proprius (Rexed laminae III, IV, V) –> 2nd order neuron (substance P = ntmtr) –> Decussation anterior commissure –> ascends in spinothalamic tract –> THALAMUS –> synapse with 3rd order neurons which relay nociceptive information to the somatosensory cortex
FACE
Nociceptor –> 1st order neuron (Ad or C) –> TRIGEMINAL NUCLEUS (brainstem) ‘the equivalent of spinal cord dorsal columns’ –> second order neuron (substance P nrtmtr) –> decussation and ascend through brainstem to THALAMUS –> 3rd order neurons relay sensory information to somatosensory cortex.
Describe the trigeminal nucleus in the brain stem
Very large extending from medulla to midbrain. So from bottom to top it is classified into the following components:
- Spinal trigeminal nucleus
- -> Pain/Temp from face - Main trigeminal nucleus
- -> Touch/proprioception from face - Mesencephalic (Midbrain) trigeminal nucleus
- -> Proprioception from jaw
What is the name of the neurotransmitter between 1st order and 2nd order neurons
Substance P
Why don’t some soldiers feel the pain of their traumatic limb amputations?
Due to pain modulation:
- Segmental inhibition
- Endogenous opioid system
- Descending inhibition
What is segmental inhibition
Reduced pain intensity from rubbing an injured area was previously (now disproven) explained by the gate theory of pain control.
Gate theory:
Previous belief that C carried pain and A delta carried touch/pressure vibration.
Previous belief that C and Ad converged on the same 2nd order interneuron and greater activity of Ad –> reduced transmission of pain.
Subsequent evidence that Ad fibres transmit pain via independent 2nd order neurons
Where are opioid receptors found
- CNS
- -> Cerebral cortex
- -> Thalamus
- -> Tractus solitarius
- -> Periaqueductal grey matter - Spinal cord
- GIT
- Peripheral afferent nerve terminals
- Other organs
Describe and classify opioid receptors
Memory aid: First Dop (OP 1) then the Kops (OP2) throw you in the van then Mop up the mess (OP3) ... NOP (never again)
Mew (OP3)
- Morphine (Prototype stimulant)
- 2 subtypes
- Mew 1 subtype: analgaesia, miosis, euphoria
- Mew 2 subtype: Resp dep, bradycardia, GIT slowed
- Supraspinal analgaesia: act at brain level
- Causes physical dependence
Kappa (OP2)
- Ketocyclazizine (prototype)
- 3 Subtypes
- Sedation/miosis/resp dep/inhibit ADH release/analgaesia
- Spinal level
- different type of physical dependence
Delta (OP1)
- Enkephalin (prototype)
- 2 subtypes
- Analgaesia and respiratory depression
- act at spinal level
Nociceptive (NOP)
- New receptor recently discovered
Sigma receptor –> does meet all necessary criteria to be classified as an opioid receptor –> naloxone does not reverse effects of its stimulation
Name the endogenous opioids and state their mechanism of action
Enkephalins
Endorphins
Dynorphin
These opioids bind to mew, kappa, delta receptors –> activation of inhibitory G protein linked transmembrane receptors –> reduced intracellular cAMP (inhibition of adenylate cyclase) –>
- Post-synaptic cell membrane K+ channel opening –> hyperpolarization of 2nd order neuronal membrane
- Inhibiton of Ca+ influx into presynaptic terminal –> reduced ntmtr (substance P) release
What is descending inhibition
Neurons from the periaqueductal grey area in the midbrain DESCEND via the raphe nuclei in the brainstem to the dorsal horn of the spinal cord where they influence the activity of ascending 2nd order nociceptive neurons, the perception of pain is reduced.
Main neurotransmitters are serotonin and Noradrenalin
–> SSRI’s, SNRI’s, TCA’s analgaesic properties
Describe the mechanism of analgaesia of the alpha 2 agonists: clonidine and dexmedetomidine
Augmentation of the activity of the descending pathway (periaqueductal grey –> raphe nuclei –> Dorsal horn –> modulate 2nd order nociceptive interneurons)
What is referred pain. Describe the mechanism of referred pain and give common examples
The brain perceives pain originating in an area other than the site of the painful stimulus.
Mechanism:
Visceral C fibres converge on the same second order interneurons as the first-order neurons from cutaneous nociceptors –> brain may therefore perceive the visceral pain as coming from the cutaneous region innervated by these cutaneous first order neurons
E.g.
- MI - Left arm/jaw
- Pancreatitis - back
- Appendicitis - umbilicus
- Diaphragm - shoulder tip
What is referred pain. Describe the mechanism of referred pain and give common examples
The brain perceives pain originating in an area other than the site of the painful stimulus.
Mechanism:
Visceral C fibres converge on the same second order interneurons as the first-order neurons from cutaneous nociceptors in the substantia gelatinosa of the DORSAL HORN of the SC –> brain may therefore perceive the visceral pain as coming from the cutaneous region innervated by these cutaneous first order neurons
E.g.
- MI - Left arm/jaw
- Pancreatitis - back
- Appendicitis - umbilicus
- Diaphragm - shoulder tip
Define hyperalgaesia and allodynia
Hyperalgaesia - increased pain from a stimulus that normally provokes pain
Allodynia - pain due to a stimulus that does not normally provoke pain (light touch or cold breeze)
Differentiate primary from secondary hyperalgaesia
PRIMARY
- Occurs in damaged tissues
- Substance P, bradykinin, histamine at site of tissue injury sensitize nociceptors decreasing their threshold potential for generation of AP’s
SECONDARY
- Occurs in tissues surrounding damaged tissues
- Increased substance P and glutamate release from activated 2nd order interneurons –> sesitize neighbouring 2nd order interneurons. Somatotropic organization of brain and SC mean hyperalgaesia is experienced in surrounding tissues.
What is the suggested mechanism for allodynia
Re-organization of circuitry in the spinal cord so that interneurons serving nociceptors are exchanged with interneurons transmitting mechanoreceptor impulses
What is neuropathic pain
Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system.
PNS: Diabetes / Infections (herpes zoster) / invasion by cancer
CNS: Multiple sclerosis or spinal cord injury
compare nociceptive pain to neuropathic pain
Nociceptive: Sharp, aching, constant
Neuropathic: Electric shock, burning, episodic (paraesthesias)
How does diabetes cause neuropathic pain
Microvascular complications associated with diabetes –> diabetic neuropathy. Ischaemia of myelinated nerve fibres causes demyelination –> exposed axon fires ectopic action potentials which are perceived as shooting or burning pain.
How does a transected nerve axon cause neuropathic pain
Attempt to regrow –> Schwann cells release nerve growth factor –> but regrowth is disorganized and sprouting nerve endings may generate spontaneous action potentials or may have altered threshold potentials
What is complex regional pain syndrome (CRPS)
Trauma damages SNS nerves too. unknown pathophysiology but a small number of these patients develop complex regional pain syndrome with chronic abnormalities at the site of injury including:
- Vasomotor changes (Hotter/Colder vs other side)
- Sudomotor changes (Reduced sweating)
- Reduced hair/nail growth
- Osteoporosis underlying bone
- Neuropathic pain - hyperalgaesia and allodynia are common
