LECTURE 9: PAIN SYNDROMES

syndrome

collection of signs and symptoms where we don’t know the cause

disease

something with a known cause, recognizable and discreet symptoms

pain in different parts of the body are comorbid with each other

diagnosis, with same signs and symptoms, can be different depending on which specialist you go see

gastroenterology speciality

irritable bowel syndrome, non-ulcer dyspepsia = syndromes commonly seen by this specialist

gynaecology

premenstrual syndrome, chronic pelvic pain = syndromes commonly seen by this specialist

rheumatology

fibromyalgia = syndromes commonly seen by this specialist

cardiology

atypical or non-cardiac chest pain = syndromes commonly seen by this specialist

respiratory medicine

hyperventilation syndrome = syndromes commonly seen by this specialist

infectious disease

chronic (postviral) fatigue syndrome = syndromes commonly seen by this specialist

neurology

tension headache

dentistry

temporomandibular joint dysfunction, atypical facial pain

ear, nose and throat

globus syndrome

allergy

multiple chemistry sensitivity

3 types of clinical pain

1. acute pain
2. cancer pain


1. oncologist
2. palliative care
3. chronic non-cancer pain


1. inflammatory
2. neuropathic
3. idiopathic/functional - no specific cause
4. headache

causes of acute pain

* burns
* fracture
* dental pain
* back pain
* acute back pain: 6-7 weeks
* sub acute back pain: 7-12 weeks
* chronic back pain: more than 12 weeks

input of nociceptors happens on 2 occasions

1. nociceptors are activated when skin and muscle are cut
2. nociceptors input information from the inflammation after waking up from anaesthetic/ post-surgery inflammation

difference between analgesic and anesthetic

* Analgesic = relief of pain
* Anesthetic = loss of physical sensation

postsurgical pain prevention by scott reuben

* he claimed that analgesic before surgery would entail no pain after waking up
* above claim = false
* nociceptors can’t fire because you’re anesthetized

if postsurgical pain doesn’t go away after 3 months

this is now considered chronic postsurgical pain

Different surgeries and possibility of getting CPSP

* cosmetic surgery leads to 21-50% chance of CPSP
* breast augmentation → 13% of developing CPSP
* vasectomy → 15% of developing CPSP

acute-to-chronic pain transitioning

2 leading theories


1. pain persists and transitions into chronic pain

chronic pain might be independent of the acute pain and starts independently of the acute pain

what is responsible for the chronification of back pain

* cortical shrinking/thinning of the brain
* gray matter volume decreases

study done by Baliki et al

2 groups of people


1. those with subacute back pain (lasting 7-12 weeks)
2. no back pain

Found 2 subgroups


1. subacute back pain resolving → cortex didn’t shrink
2. subacute back pain progressing/persisting → gray matter of cortex shrinking

prevalence of cancer pain depends on what?

the type of cancer

* primary cancers are more painful
* i.e. oral cancer = very painful; leukemia unlikely to be painful

true or false: cancer pain metastasizes into bone

* true
* pain is always an issue with cancer patients
* the timeframe for when pain becomes an issue varies

breakthrough pain

sudden and brief flare-up of pain from chronic condition

how is cancer pain managed

* by 1 drug that managed to work well enough against average cancer pain
* 2nd drug administered to manage breakthrough pain

side effects of chemotherapeutics

* painful neuropathy (damage to the peripheral nerves)
* it is called chemotherapy induced peripheral neuropathy→ CIPN
* Pain becomes too much => chemotherapeutics have to be reduced

\*reminder\* higher dosage of chemotherapeutics = higher success in treating ppl’s cancers

what causes cancer pain?

multiple causes such as:

* inflammation from the immune system attacking the tumour
* tumour is pressing on nerves
* tumour is disrupting nearby tissue
* tumours release algogens

what is arthritis

chronic inflammatory pain that occurs in joints

describe a normal joint

* cartilage: cushion/shock absorber so that the bones don’t hit each other
* synovial fluid which is kept inside by the synovial membrane that keep the cartilage together

2 types of arthritis

1. osteoarthritis (disease of old age)
2. rheumatoid arthritis (can occur in younger people)

osteoarthritis causes

* more common than rheumatoid arthritis
* disease of old age
* cartilage degrades and gets thinner causing bones to rub

OR

* synovial fluid leaks out of membrane causing bones to hit

rheumatoid arthritis cause

* can occur in younger people
* autoimmune disease: immune system is attacking your own tissue
* leads to inflammation

What leads to inflammation in RA?

1. ^^proteins such as macrophages and monocytes release TNF-a and interleukin-1 → cause tissue damage^^


1. these are cytokines that trigger the immune system response
2. TNF-alpha → inflammation
3. IL-1 is → cartilage and bone destruction + impeding cartilage repair

arthritis leads to

* pain
* disability
* severity of arthritis is not indicative of the amount of pain

rheumatoid arthritis treatment

* monoclonal antibodies

how do monoclonal antibodies help RA?

* they are TNF-alpha blockers
* w/o TNF-alpha
* less tissue damage
* less inflammation

examples of TNF-alpha blockers

* AKA monoclonal antibodies
* infliximab
* etanercept
* adalimumab
* certolizumab
* golimumab

why are monoclonal antibodies injected and not made into pills

* the molecules are too big to be made into pills
* allows physicians to see side effects while patient is being administered drugss

treatment for osteoarthritis

* NSAID
* opioids

causes of chronic neuropathic pain

* nerve trauma
* iatrogenic nerve injury
* caused by the medical treatment itself (i.e. surgeon nicks a nerve while performing mastectomy)
* nerve compression
* parasitic, bacterial or viral infection
* inflammation (sterile)
* metabolic/ nutritional/ ischemic
* toxic
* ionizing radiation
* hereditary neuropathies
* autoimmune, idiopathic

example of nerve trauma

* stump pain
* phantom limb
* CRPS2 (complex regional pain syndrome II) = causalgia: intense burning
* bone fractures
* penetrating injuries

\

examples of iatrogenic nerve injury (surgery, radiotherapy, chemotherapy)

* scar pain
* post-thoracotomy pain
* a surgical procedure in which a cut is made between the ribs to see and reach the lungs or other organs in the chest or thorax.
* ==post==-mastectomy pain
* accident intraneural injection
* vincristine (a chemotherapy drug) neuropathy

examples of nerve compression due to entrapment

* carpal tunnel (occurs when nerves are compressed in wrist)
* ulnar nerve entrapment
* occurs when the ulnar nerve in the arm becomes compressed or irritated
* foraminal (lateral) stenosis
* Each of the 33 bones of the spine has a large central opening for the spinal cord. Additional openings called foramen, which can get clogged, allow the nerves branching from the spinal cord to travel to the arms, legs and other parts of the body.

examples of compression due to tumor, artery, edema (swelling caused by too much fluid), herniated intravertebral disc

* cancer pain
* sciatica (pain, weakness, numbness, or tingling in the leg) caused by compression on sciatic nerve


* trigeminal neuralgia (type of chronic pain disorder that involves sudden, severe facial pain) caused by compression of the trigeminal nerve

examples of parasitic, bacterial or viral infection

* nerve abscess (hole)
* Hanson’s disease (leprosy) infection caused by slow-growing bacteria called Mycobacterium leprae
* tabes dorsalis caused by untreated syphilis infection
* postherpetic neuralgia
* HIV/Aids neuropathy

examples of inflammation

* acute and chronic demyelinating neuropathy
* dorsal root ganglionitis
* tumor infiltration of nerves or innervated tissues

examples of metabolic/nutrional/ischemic

* diabetic neuropathy
* sickle cell anemia
* occlusive/ischemic angiopathy
* alcoholic neuropathy
* vitamin deficiency

toxins

* lead
* mercury
* ethanol
* vincristine neuropathy
* other chemotherapeutics

example of ionizing radiation

* radiation burns
* radiation therapy for cancer

examples of hereditary neuropathies

* some Marie-Carcot-Tooth neuropathies (group of disorders that cause damage to periphiral nerves)
* Fabry’s disease (a serious genetic disorder that can lead to life-threatening heart and kidney problems)

examples of autoimmune, idiopathic

* Guillain-Barré
* small fiber

sensory deficits associated with neuropathic and nociceptive pain

* neuropathic pain: numbness, tingling, pricking
* nociceptive pain: uncommon to have sensory deficits

hypersensitivity in neuropathic vs nociceptive pain

* neuropathic pain: leads to allodynia (pain evoked by non-painful stimuli) or hyperalgesia (increased sensitivity to pain)
* nociceptive pain (pain to tissue): uncommon except for hypersensitivty surrounding area of acute injury

how does pain move in neuropathic vs nociceptive pain

* neuropathic pain: distal radiation (moving pain from center to the extremities)
* nociceptive pain: distal radiation less common

paroxysms (a sudden attack) for neuropathic vs nociceptive pain

* neuropathic pain: worsening is common and unpredictable
* nociceptive pain: worsening is less common and associating with activity

autonomic signs (part of the nervous system that controls __muscles of internal organs__ such as the heart, blood vessels, lungs, stomach, and intestines; and __glands__ such as salivary glands and sweat glands) for nociceptive vs neuropathic pain

* neuropathic pain: color changes, temperature changes, swelling, sweating occur in 1/3 to 1/2 of patients
* nociceptive pain: uncommon

Painful diabetic neuropathy (PDN)/diabetic peripheral neuropathy (DPN)

nerve damage caused by untreated diabetes

how does diabetic peripheral neuropathy damage tissue

* healthy tissue is damage due to capillary damage (no blood supply)
* leads to nerve damage
* leads to numbness + pain
* injury becomes more common (due to numbness and pain)
* injury can get infected which can lead to amputation

why is painful diabetic neuropathy worse in feet

* feet (most extremities) already get very low blood circulation
* the above is worsened with age
* this causes PDN to be more common in feet
* glove and stock distribution

shingles

* caused by a complication after chicken pox infection (varicella virus)
* virus goes dormant in one of the dorsal root ganglia
* becomes active
* causes rash
* \

post-herpetic neuralgia

* complication of shingles
* pain lasts long after the rash goes away

phantom limb pain

* results after an amputation
* neuropathic pain syndrome

\

phantom limb pain (PLP)

* over 50% of amputations are caused by diabetes complications
* second cause of amputations = peripheral artery disease (PAD)
* amputation is not NECESSARY for PLP
* certain individuals born w/o limbs can also experience PLP

study by Davidson et al

* upper limb pain presents more serious pain, severity and frequency compared to lower limb pain

phantom limb symptoms

* shooting, stabbing, burning, cramping
* can also feel heat/cold
* can feel movement of phantom limb
* change of size
* can feel itch
* phenomenon of telescoping (feeling of limb retracting into body)
* phantom hand can’t be opened, stays clenched as a fist

referred pain

**pain** that's originating from a different location in your body is felt elsewhere.

causes of phantom limb pain

2 schools of thought, changes in the brain happening


1. central changes (brain + spinal cord)
2. peripheral changes (nerves that branch off from spinal cords to different parts of the body)

Cortical reorganization (changes happening centrally)

* people with PLP, area of the cortex that is responsible for amputated limb can take over the function of other body parts
* how was the above discovered?
* people with PLP pursed their lips and motor cortex area responsible for phantom limb lit up

PLP interventions (hypothesis for peripheral nervous system)

* lidocaine eliminated PLP in amputees suggesting that its primary driver is hyperexcitable afferent neurons rather than maladaptive cortical plasticity.
* mirror box theory

mirror box theory

* phantom limb pain reduced
* involves putting in functioning arm in a box that has a mirror
* mirror therefore, reflects the functioning arms movements
* supposedly provides relief to individuals with PLP
* tricks the brain because it gives the illusion that the amputated limb is not missing
* cannot be replicated => mirror therapy = ineffective

how does lidocaine work

* prevents pain by blocking the signals at the nerve endings in the skin

Complex regional pain syndrome

2 types


1. CRPS I (RSD = reflex sympathetic dystrophy)
2. CRPS II (Causalgia)

CRPS I (RSD) characteristics

* pain is circumferential
* responds well to sympathetic blocks
* used to treat pain involving nerves from the sympathetic nervous system
* no response to nerve blocks
* thermal and mechanical allodynia
* ==allodynia==: pain due to a stimulus that normally doesn’t provoke pain
* leads to swelling, redness and change in skin temperature

CRPS II (causalgia)

* discrete nerve distribution
* since only 1 nerve is damaged
* variable response to sympathetic block
* responds well to nerve block
* mechanical allodynia

Which type of CRPS is this?

CRPS II - Causalgia

What are some possible causes of CRPS I?

* inflammation
* central sensitization
* cortical plasticity
* sympathetic processes
* psychological factors
* genetic predisposition
* peripheral sensitization

fibromyalgia

* nociplastic disorder
* pain that arises from altered nociception
* no inflammation, no nerve damage, no tissue damage

\

prevalence of fibromyalgia

* circles → women
* squares → men
* characterized by chronic widespread pain + fatigue
* affects 7% of women

fibromyalgia tender points

* rheumatologists would press on tender points
* if tender points hurt + fatigue => fibromyalgia
* how it was diagnosed previously

windup pain in patients with fibromyalgia

windup pain = phenomenon in which pain signal increases and fires more frequently

\

2 competing theories of windup pain in FS

1. increase in ascending transmission


1. The pathway that goes upward carrying sensory information from the body via the spinal cord towards the brain
2. too much info being carried to the brain
2. decrease in descending emission


1. the descending pathway inhibits pain

decreased conditioned pain modulation in fibromyalgia

* women with FMS have impaired conditioned pain modulation
* CPM = psychophysical assessment used to estimate the efficiency of an individual's central nervous system which reduces or augments pain
* CPM used as a predictive assessment for the development of chronic pain and responses to pain interventions

through which test was it discovered that women with FMS have impaired conditioned pain modulation?

* through cold pressor test
* CPT → used for examining pain threshold and tolerance by subjects placing their forearm in an ice bath

is fibromyalgia really small-fiber neuropathy?

* density of nociceptors nerve endings of those with FMS is less dense
* as if they have a neuropathy selectively affecting small fibers such as the nerve endings of the nociceptors

overlap between idiopathic pain conditions

\*reminder\* idiopathic = we don’t know

* idiopathic pain conditions share symptoms
* different presentation of the same thing

conditions comorbid with fibromyalgia

PEOPLE with FMS are more likely to get

* IBS
* TMJ
* anxiety
* osteoarthritis
* carpel tunnel
* etc.

pain location in idiopathic pain syndromes

2 studies


1. IBS


1. lower threshold to shoulder pressure
2. lower threshold to pressure to fingernails
3. lower heat pain threshold

why do they have lower sensitivity if they have IBS?

→ cause they also have FMS


1. vestibulodynia = allodynia of the vulvar vestibule


1. lower threshold to other place

conclusion: people with these conditions actually have widespread pain

4 types of headaches

1. cluster → pain socket
2. sinus → pain in sinus cavity
3. tension → across forehead
4. migraine

characteristics of migraines

* pulsating
* more severe
* activity make it worse
* nausea
* vomit
* photophobia and phonobia = sensitivity to light and sound
* can be disabling because pain forces you to withdraw
* 4-72 hours

tension headaches

* pressing/tightening
* no aggravation due to physical activity
* no nausea or vomit

4 stages of migraine

1. prodrome


1. happen before the actual migraine
2. photophobia or phonobia
3. few days before
2. aura


1. right before the migraine
2. an hour before
3. headache
4. post-drome


1. pain is gone
2. reminder that migraine occurred such as tender scalp, mood change

aura/cortical spreading depression

* wave of electrical excitability
* starts at the back of the brain where the occipital cortex is and waves forward
* neurons fire but then they get depressed and can’t fire

cause of aura

cortical spreading depression

* experiement done where speed of aura matches the speed that CSD moves
* CSD might not actually cause the pain of migraine

how mant migrainers are affected by aura?

20%

cause of migraine

1. vasodilation
2. neuronal