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Flashcards in 6 Mechanisms of Pain Deck (17):
1

Pain (p.4)

  • Pain
  • # of neurons to relay pain information from the periphery to the cortex
  • nociceptors
  • The purpose of pain
  • Persistent or chronic pain

  • Pain is the perception (i.e. Pain is in the Brain) of noxious or potentially damaging stimuli.
  • It takes three neurons to relay pain information from the periphery to the cortex.
  • Peripheral sensory neurons (the first neuron in the chain) that are dedicated to detecting pain are called nociceptors.
  • The purpose of pain is to get you to alter your behavior or attend to a situation.
  • Persistent or chronic pain
    • Pain (often ongoing) that occurs in the presence or absence of observable pathology.
    • can be produced by changes anywhere in the pain pathway.

2

Pain (p.4)

  • For the GI tract (and most other systems)
    • the first neuron
    • the second neuron
    • the third
  • There is an additional pathway for visceral pain 
  • Nociceptors
    • usually/
    •  respond to/

  • For the GI tract (and most other systems)
    • the first neuron is the primary afferent neuron located in spinal or inferior vagal ganglion
    • the second neuron is in the spinal cord dorsal horn or brainstem (NTS),
    • the third is in the thalamus (a hideously complex potato-shaped structure in the diencephalon)
  • There is an additional pathway for visceral pain
    • Dorsal Column Pathway that makes an additional stop in the dorsal column nuclei, e.g. nucleus gracilis
  • Nociceptors
    • usually unmyelinated and slower (aka C-fiber) or lightly myelinated and faster (A∂ fiber).
    •  respond to noxious mechanical stimulation (aka high threshold mechanical stimulation) and/or noxious heat (fire), noxious cold, or chemical (pH) stimuli.

3

Pain

  • Adequate stimulus
  • This may not be true for gut visceral afferents
    • because/
    • professional nociceptors

  • Adequate stimulus
    • there are different types of sensory neurons and each responds to a unique class or type of stimulation.
    • For nociceptors, the hallmark is the ability to respond only (fire action potentials) to high threshold mechanical/temperature (e.g. a pinch, fire, ice) or noxious chemical (acid) stimulation.
  • This may not be true for gut visceral afferents
    • because many (perhaps the majority) can detect both noxious and non-noxious stimuli;
      • the GI tract is heavily innervated by sensory neurons that can do more than one job.
    • But, the GI tract also has professional nociceptors; those neurons that only detect noxious stimuli.

4

How could pain information be transmitted in the absence of dedicated pain fibers? (p.8)

  • Frequency Coding
  • Silent afferents
  • the two choices above do not begin to consider/
  • Visceral hypersensitivity
    • Hypersensitivity (allodynia)
    • Hyperalgesia

  • Frequency Coding
    • low frequency firing pattern is interpreted by the CNS as normal function.
    • At high frequency, stimulation is perceived as pain.
  • Silent afferents
    • In the bladder there are sensory fibers that do not normally fire even at potentially noxious levels of stimulation.
    • Following inflammation, these fibers may be active even during normal micturition and may produce painful sensation.
    • These fibers would be a special class of sensory neurons that would be classified as nociceptors.
  • the two choices above do not begin to consider changes that could (and probably do) occur in the spinal cord and brain
    • Changes in primary afferents may be the first step in changes that occur throughout the pain pathway
  • Visceral hypersensitivity and why can it be so debilitating
    • Hypersensitivity (allodynia) is when normal sensations, which in the case of visceral input may be only subconscious, become painful
    • Hyperalgesia is when painful stimuli become more painful.
      • Example: Irritable Bowl Syndrome (IBS).

5

Visceral Pain Comorbidities

  • Depression
    • persistent visceral pain can lead to depression, depression can cause pain, and each condition can exacerbate the other.
  • Nausea
    • Primarily the domain of vagal afferents
    • #1 reason that chemotherapies are aborted, even more so than vomiting
  • Cachexia
    • Weakness, fatigue and muscle loss.
    • Can accompany pain,
    • negative symptom for any GI disorder, especially GI cancers.
  • Poor sleep hygiene
    • Pain can degrade sleep leading to overall decline in quality of life.

6

Sensory Pathways for Visceral Sensation (p.11)

  • There are two ways sensory information travels from the viscera of the GI tract to the brain:
  • Components of the Vagus nerve include:
    • Visceral motor output from the/
    • Somatic motor output from the/
    • Somatic sensory neurons located in/
    • Visceral sensory neurons located in/

  • There are two ways sensory information travels from the viscera of the GI tract to the brain:
    • Vagal visceral afferents
    • Spinal visceral afferent
  • Components of the Vagus nerve include:
    • Visceral motor output from the dorsal motor nucleus (DMN) of the vagus.
    • Somatic motor output from the nucleus ambiguus.
    • Somatic sensory neurons located in superior vagal ganglion that project to trigeminal nucleus
    • Visceral sensory neurons located in the inferior vagal ganglion (aka nodose) that project to the nucleus tractus solitarius (nTS)

7

Vagal Visceral Pathways (Cranial Nerve X):
Other important (i.e. testable) tidbits about the Vagus

  • Vagus means/
  • It is 80-85%/
  • Vagal visceral sensory fibers probably do not/
  • Moreover, visceral sensory information carried in the vagus does NOT/
  • How do we know this? (Hint: which patient population could provide insight into this issue?)
  • Visceral afferents encode/
  • The vagus provides sensory fibers to/
  • The sensory component of the vagus nerve/

  • Vagus means “wanderer”.
  • It is 80-85% sensory.
  • Vagal visceral sensory fibers probably do not carry "pain" information for the gut (it may transmit pain for organs of the thoracic cavity).
  • Moreover, visceral sensory information carried in the vagus does NOT reach consciousness.
    • It may be associated with general feelings like hunger, satiety, nausea, as well as emotional components of visceral pain.
  • How do we know this? (Hint: which patient population could provide insight into this issue?)
    • Paraplegics with cervical complete spinal transections still detect pain
    • No sensory input from the parasympathetic nervous system
    • The only thing that's intact b/n gut and brain is the vagus nerve
  • Visceral afferents encode physical and chemical events (distension, contraction, pH) and relay this information back to the CNS to modulate function.
  • The vagus provides sensory fibers to organs from the pharynx to the splenic flexure.
  • The sensory component of the vagus nerve is NOT part of the parasympathetic nervous system.
    • The sensory fibers “run with” the parasympathetic preganglionic fibers but belong to a different functional system.

8

Spinal Visceral Sensory – Conscious Pain (greater splanchnic nerve) (p.14)

  • Sensory fibers originate/
  • Only 1-2% of all spinal sensory neurons innervate
  • Sensory fibers must/
  • For the sympathetic system, sensory fibers run with/
  • For the parasympathetic system, sensory fibers run with/
  • You can do sensory nerve blocks by/

  • Sensory fibers originate in the spinal or dorsal root ganglia.
  • Only 1-2% of all spinal sensory neurons innervate viscera.
  • Sensory fibers must “hitch a ride" with components of the sympathetic nervous system and the sacral portion of the parasympathetic system.
    • They do not belong to either system!
  • For the sympathetic system, sensory fibers run with the greater (T5 to T 8) splanchnic nerve, the lesser (T10 to T11) splanchnic nerve, the least (T12) splanchnic nerve , the lumbar splanchnics (there are usually 4 in humans), and sacral splanchnics.
  • For the parasympathetic system, sensory fibers run with pelvic splanchnic nerves that also contain preganglionic parasympathetic fibers.
  • You can do sensory nerve blocks by injecting neuroactive agents into prevertebral ganglia or plexus.

9

Comparison of Sources of Sensory Innervation of viscera (p.16)

  • Dual innervation for sensory fibers to the gut
  • what's associated with abdominal dysfunction

  • Dual innervation for sensory fibers to the gut
    • Spinal (“Sympathetic”)
    • Craniosacral (“Parasympathetic")
  • Composite sensation of pain, nausea, fear, and discomfort u

10

Referred Pain (p.17-18)

  • ?
  • Caused by/
  • intense visceral sensory input may be perceived as/
  • Take home message

  • the sensation of pain in somatic structures as the result of pain impulses arising in visceral structures.
  • Caused by the sharing of second order sensory neurons in the dorsal horn.
    • virtually every second order sensory neuron that receives visceral input can also be stimulated by stimulation of somatic tissues.
  • intense visceral sensory input may be perceived as arising from some portion of the abdominal wall instead of the affected organ.
  • Take home message: Single visceral (in this case spinal) afferent projects to a large number of spinal neurons making it very likely that synaptic activity generated by this fiber will overlap with somatic sensation.

11

Referred Pain Locations (don't memorize!)

  • The abdomen can be divided into/
  • The location of referred pain from different pathologies/

  • The abdomen can be divided into four quadrants plus the central region.
  • The location of referred pain from different pathologies is somewhat reproducible and can be useful for diagnostic purposes.
  • Right lower quadrant:
    • Acute appendicitis
    • Mesenteric lymphadenitis
    • Infective distal ileitis
    • Crohn’s disease
    • In women:
      • Ectopic pregnancy
      • Ruptured ovarian cyst
      • Acute salpingitis
    • Renal disorders
      • Right ureteric calculus
      • Acute pyelonephritis
    • Acute cholecystitis
    • Acute rheumatic fever
    • Pyogenic sacroiliitus
  • Right upper quadrant:
    • Acute cholecystitis
    • Biliary colic
    • Acute hepatic distension or inflammation
    • Perforated duodenal ulcer
  • Central abdominal pain
    • Gastroenteritis
    • Small intestinal colic
    • Acute pancreatitis
  • Left upper quadrant
    • Perisplenitis
    • Splenic infarct
  • Left lower quadrant
    • Acute diverticulitis
    • Pyogenic sacroiliitis

12

Best pain therapy

  • Address underlying mechanism
  • Pharmacotherapies will only work temporarily

13

#1 risk factor for pancreatitis & NSAIDs

  • Pancreatitis: smoking (alcohol not so much)
  • NSAIDs: liver toxicity

14

To decrease pancreatic secretions (p.22-23)

  • Proton-pump inhibitors
  • Oral pancreatic enzymes
  • SubQ octreotide
  • Nerve block
  • Whipple procedure

  • Proton-pump inhibitors - increases duodenal pH and thus decrease stimulus for pancreatic excretion – unlikely to work but safe.

  • Oral pancreatic enzymes – not clear why they work, but it may involve feedback mechanism via a decrease in CCK release.

  • SubQ octreotide – (mimics somatostatin) inhibits release of gastrin, CCK, glucagon, VIP, GH and pancreatic polypeptide.  Mixed results from at least 3 small studies.  Expensive and painful in some patients.

  • Nerve block - inject local anesthetics or toxins (alcohol, phenol) to silence sensory neurons.

  • Remove most of the pancreas via Whipple procedure

15

IBS

  • Check patients who are coming in with IBS-like symptoms for/
  • Treatment for IBS

  • Check patients who are coming in with IBS-like symptoms for Celiac disease
  • Treatment for IBS
    • Oxycodone
    • Low dose anti-depressants
      • TCAs: amitriptyline (Elavil)
      • SSRIs: Sertraline (Zoloft), Fluoxetine (Prozac)
    • Smooth muscle relaxants: anti-muscarinics (hyoscine, levsin)
    • 5-HT4 agonist (Tegasrod, Zelnorm)
    • Anticonvulsants: neurotinin (gabapentin)

16

Furor medicus (p.26)

  • Both patients and physicians enter into a relationship where they want to solve the problem
  • When they can't solve the problem, both get frustrated
  • You then start trying to do things
  • Sometimes you go overboard
  • Once you start adding narcotics, you can get Narcotic Bowel Syndrome
    • Start getting resistance to the opiods, so start taking more
    • Patient gets frustrated b/c nothing's working
  • End up coming into the hospital for a procedure
    • Start taking out organs
    • Everybody ends up getting frustrated
  • Then you get maladaptive therapeutic interaction
    • Spirals downhill

17

Take home messages

  • Only 30% of chronic pain patients/
  • Solution/
  • Next best solution

  • Only 30% of chronic pain patients (GI or otherwise) get long-term relief with opioids. 
  • Solution:  treat underlying disease whenever possible. 
  • Next best solution – non-pharmacologic treatments – Cognitive behavioral therapy, diet, exercise etc.