W11 Pain and Motor Control and disease Flashcards
Loss of pain
Loss of pain sensation due to nerve damage is a feature of diabetes mellites adn leprosy. Absence of pain means a person is unaware of minor injury. Unless carefully managed, these injuries become infeted; in the case of leprosy: can lead to loss of fingers, toes or entire limbs.
What is pain?
Differs from the classical senses (vision, hearing, touch, taste, smell) because it’s both discriminative sensation and a graded motivation.
It’s a leading clinical complaint that can present mystifying symptoms, such as allodynia, referral, placebo-effect, after-sensations, emotional variability and hyperpathia.
It can attain intolerable intensity, can disappear in the heart of a battle
Specificity Theory
Ambiguity about pain is reflected in ow we think about its repesentation in the brain.
Specificity theory: holds that pain is a distinct sensation, detected and transmitted by specific receptors and pathways to distinct pain areas of th ebrain.
Convergence thoery
Suggests that pain is an integrated, plastic state represented by a pattern of convergent somatosensory activity within a distributed network.
What are afferent neurons with free nerve ending?
Nociceptors.
Classified according to activating stimlus, fiber-tpe and conduction velocity.
Lightly myelinated A[delta] fibers
fast ~20m/s: mechano sensitive and mechanothermal sensitive
Unmyelinated C fibers
slow ~2m/s = Polymodal: mechanical thermal and chemical
What neuron responses specificially to pain
Nociceptors respond specifically to pain and are a subset of afferents with free nerve endings.
Thus, there are a distinct set of A[delta] and C fibers, nociceptors, specifically associated with pain detection.
Fast pain
Fast, first pain: sharp and immediate, can be mimicked by direct stimulation of A[delta] fiber nociceptors.
Slow pain
Slow or ‘second’; more delayed, diffuse and longer lasting; mimicked by stimulation of C fiber nociceptors.
Molecular pain receptors
Specific molecular receptors associated with nociceptive nerve ending are activated by heat.
The capsaicin receptor (TRPV1) is activated in nociceptive A[delta] and C fibres at 45°C and by capsaicin, a vanilloid which is the active component in chilis. Related receptors are activated in A fibres alone at even higher thresholds (52°C)
Central pain pathways
Pathways carrying nociceptive information, not the brain are complex. Two components:
1- Sensory discriminative: signals location intensity and type of stimulus.
2- Affective motivational: signal unpleasantness and enables autonomic activation, classic flight or fight response.
Discriminative pathway is easiest to define and involves a tract we have already met: the spinothalamic tract, also called the anterolateral system.
What does Spinothalamic prokections preserve?
Topology. Measurement of activity in the somatosensory cortex indicate that this region does indeed respond to painful stimuli and that rsponse correlates to intensity of pain. That this is spatially mapped, shown ecperimentally.
Comparison (MRI) of cortical activation by painful (C fibre) or innocuous mechanical (vibration 1 [beta] fiber)
stimuli to skin demonstrates that painful stimuli activate the same region of the somatosensory cortex as the non-painful mechanical stimulation applied to the same region of skin (yellow arrows in A).
Affective-motivational pathways
Shares some pths with the anterolateral system.
Little or no topographic mapping: neurons in parabrachial nucleus an respond to painful stimuli from anywhere on the body’s surface.
Nmber of points of input to the emotional limbic and homeostatic hyopthalamus.
Strong Correlation or painful experience with activity in cingualte cortex.
Summary of the specificity theory
There are receptors, both celullar and molecular, that respond specifically to pain (a subset of A [delta] & C fibres; TRPV1). There are specific pathways that convey pain messages. There are regions of the CNS that are specifically and distinctly activated in response to pain.
Limitation - specificity theory
Pain perceived is not always proportional to intensity of stimulus. Modulation by other stimuli (e.g. acupuncture). Perception of pain in severed limbs (phantom limbs). Referral of pain from viscera to skin. Placebo effect.
Hyperalgesia
increased response to a painful stimulus. Hypersensitivity of damaged skin to a normallly tolerable painful stimulus. (e.g. light skin rpick)
Allodynia
Painful response to a normally innocuous stimulus. Painful sensitiivity of sunburnt to skin to gentel mechanical stimuli
What is the inflammatory response - peripheral effects
Peripherally, tissue damage relase a soup of inflammatory substances which affect nerve function, recruit mast cells and neutrophils and increase local lood flow.
Prostaglandins lower the threshold for axon potential generation. Some painfkiller (analgesics) e.g. aspirin act on Cycloocygenase, an enzyme important in prostaglandin biosyntheisis.
Central sensitisation
result from the acitivity dependent local release of sustances like prostaglandins from nociceptive dorsal horn neurons.
This can lower the thresholds fro action potentials generation for neurons relaying nociceptive inforamtion, also giving rise to hyperalgesia.
Consequence: relay neurons also become sensitive to nervy non-nociceptive inputs, normally innocuous stimuli can be perceied as painful: allodynia
Hyperpathia
is a variant of hyperalgesia and allodynia, but its underling causes are different and so the symptoms are also slightly different.
It resutls when there is fibre/axonal loss/damage, that results in a raissing of the detection threshold.
The result however is that when the detectio threshold is exceeded the subsequent excitability I much greater and patients report explosive pain.
Phantom Limb Pain
Phantom limbs are experienced after amputation. Patients have the illusion that the limb is still present. Indicates that central representation of the body is not passive, ie that it persists in the absence of peripheral input. Surprisingly, children born without limbs can also have phantoms, suggesting that central maps may be partly pre-formed.
Referred Pain
Phenomenon not easily expalined in term of the specificity theory.
Pain due to damage in the viscera is often perceived as coming from a specific location in the sin according to what organ is affect: reffered pain.
This aids clinical diagnosis of organ dysfunction.
Central Modulation of Pain
It is clear that our perception of pain varries according to its context.
Henry Beecher, WWII: soldiers with severe battle wounds often experienced little/no pain.
Similarly the mere suggestion that pain will be relieved can result in pain relief: placebo affect.
Indicates that mechanisms exist, voluntary or involuntary, to overcome even severe pain.
Physiological basis of pain modulation
Discorved when experiements stimulating certain regions of the midbrain produced pain relief.
Stimulation of the periqueductal gray activates brainstem nuclie that modulate the activity of dorsal horn neurons (descending inputs activate enkephalin, realising interneurons inhibit nociceptive fibers)
Enkephalins
Member of a famly of endogenous opiod peptides that also include endorphins and dynorphins.
If activated, realise interneurons which presynaptically inhibt nociceptive fiber
Where could modulatio also occur?
Locally.
Rubbing an injury often relieve the pain. This is thought to be due to local inhibition by mechanoreceptors (A [beta]fibres) of nociceptive (C fibre) inputs in the spinal cord
Gate or Senosry interaction theory of pain - Melzack & Wall, 1965
Suggested pain perception to be the result of integration of convergent sensory information. The existence of such circuits is provocative, and certainly challenges the simple assumption of a ‘straight-through’ pain input that underlies specificity theory.
Motor Control hierarchy
Simple reflexes involve local circuit control of spinal motor neurons by spinal sensory neurons.
All movements produced by the skeletal musculature are initiated by these lower motor neurons.
1870 Fritsch & Hitzig - Electrical stimulation of part of the cortex
Elicits contraction of contralateral body muscle. Region became known as the motor cortex and more specifically the primary motor cortex.
The neurons found in the brain that onntorl motor function: upper motor neurons
Motor cortex - Somatotopically maps
The correlation of the site of stimulation with the location of muscle contraction and the topographic map is similar to that of the somatosensory system.
Similarities and diffferences of both sensory/motor maps
Similarities: Lower body is represented medially, upper body laterally. Proportions reflect density of innervation and behavioral significance.
Differences: the ears do not move but they do a lot of sensing
Axial muscles
Trunk movement
Proximal muscles
Shoulder, elbow, pelvis, knee movement
Distal muscles
Hands, feet, digits (finger/toes) movements
Somatic motor system basics
Control of lower motor neurons in the ventral horn of the spinal cord which innervate striated muscle to control movement. Specifically: Axial muscles, Proximal muscles, Distal muscles.
Innervation is via a specialized synapse called the Neuro Muscular Junction (NMJ)
What are the low motor neurons rules and definitions?
Each muscle fibre receives input from a single lower motor neuron. Each lower motor neuron innervates the fibres of just one muscle.
