Exam 3: Lecture 17 - Chronic Pain Management Flashcards
Where does pain start in the pain signaling pathway?
-Pain starts at the nerve endings (or nociceptors)
When the nerve endings are activated in the pain signaling pathway, that is considered ______
Transduction
What happens after transduction in the pain signaling pathway?
-Signal is transmitted through long sensory nerve fibers up to the spinal cord, passing through the dorsal root ganglion on the way -> go up to second order neurons -> perception (awareness of pain)
What is often thought of as the first location in the pain signaling pathway to modulate pain?
-The dorsal horn of the spinal cord
What is an important receptor in the spinal cord that is plugged with Mg unless excited, and is responsible for increasing glutamate flux in the dorsal horn of the spinal cord & therefore increases calcium binding and ascending pain impulses
-NMDA receptor
What can affect how we feel pain?
-Genetics & past experiences
T/F: The amplification pattern in the NMDA receptor excitation can become a pain symptom in itself
True!
How can pain affect movement?
-We tend to move the body differently if we are in pain
-So, we compensate for painful or still regions, which can lead to additional problems
What problems can compensation of pain by movement lead to?
-Support limb OA
-Myofascial strain patterns
-Tendon & ligament injury
-Altered body awareness & increased tendency toward additional injury
What condition do we study when we are studying chronic pain because it is the “easiest” in patients who cannot speak?
-OA (osteoarthritis)
There is a balance of what mediators in the immune system normally (at homeostasis)?
-Pro-inflammatory & anti-inflammatory mediators
In chronic pain, what immune system balance becomes hard to maintain (specifically)
-Balance of pro-inflammatory & anti-inflammatory mediators
-Normally expect inflammation to rise to take care of problem then expect body to pull it back together & bring it back to normal, but in chronic pain it becomes harder for the body to bring back that inflammation
Because it is harder for chronic pain patients to balance pro-inflammatory and anti-inflammatory mediators, what drug type has fallen from favor as increasingly specific targets become available?
-Broad anti-inflammatories (steroids)
What else can also be acting on the immune system in chronic pain patients?
-Age
-A lot of chronic pain is occurring in our older patients
What is an important organ system to chronic pain that is often overlooked, but growing rapidly in appreciation & research?
-Fascia (really the biggest “organ” system in the body
What does fascia connect?
-Deeper & broader bands connecting muscles & tendons
-The connection between bones
-“Interstitium” around organs & vessels (fluid in which all lymphatics & fluids not in vessels live)
What is fascia important for in chronic pain?
-Body awareness
-Unity
-Fluid balance
-Connecting the fluids back to the vascular space & thoracic duct
-Surrounding all of the organs in the body
Why is fascia important?
-Can contract & modulate body in terms of mechanosensory fine tuning
-Help w/ reflex arcs that protect joints & help run the kenematics of motions
When you don’t use your fascia enough (ex: sitting for long flight) it can become ______ which ______
-“sticky” which compounds pain & dysfunction
When fascia is not working properly you lose _____ as well
body awareness
Any inflammation in the connective tissue can lead to ____ and lack of use
Stickiness
What is really the home of the immune system?
-The connective tissue
What is the scaffolding & structural support of cancer cells and tumors?
-The connective tissue
____ improves gait, mechanical sensitivity, and connective tissue inflammation in a rodent model
-Stretching of the back
What does myofascial palpation do?
-Gives you a sense of pain as related to palpation
What is myofascial palpation?
-Palpation using light pressure so you are only manipulating the fascia
What are some (big category) chronic pain treatment?
-Pharmacology/Diet/Supplements (global, topical, regional)
-Weight optimization
-Physical medicine
What is physical medicine and what are some examples of it?
Not drugs, but can be actively used to help pain
-Touch/massage
-Acupuncture
-Laser or Photobiomodulation
-Therapeutic exercise
-Joint mobilization
-Heat/cold
-Exercise/motion
-Fascial release
What are the pharmacology analgesia for pets?
-Opiods
-NSAIDs
-Na+ Channel blockers
-Alpha-2 antagonists
-TCA’s, SSNRIs
-NMDA antagonists
-Phytochemicals w/ central effects
-Intra-articular
What are the injectable drugs (systemic with joint effects)?
-Adequan
-NGF inhibitors (librella, solensia)
What are the types of intra-articular analegesia?
-Steroid
-Hyaluronic Acid
-Biologicals
______ & ______ are in general not used much for chronic pain
Na+ channel blockers & alpha-2 agonists
Which type of analgesia?
-Poorly absorbed
-Roles in chronic pain questionable
-Neuro-inflammatory
-Poor long-term efficacy
-Increasing doses required
-Poor bioavailability
-Opiods
What happens at the same time an opiod drug is providing analgesia?
-It is also winding up the pain sensing system
(w/ chronic pain already have wound up pain sensing system so we don’t want to raise it more)
_____ = not a good choice for chronic pain management
-Opiods
____ is associated with less progression of arthritis and pain in dogs with OA
-NSAIDs
What is the problem with using NSAIDs?
-Sometimes have to wean pet off them
-Can cause significant damage to things like livers & kidneys
-Can’t always see on the surface -> have to do bloodwork to know (unless they’re really sick)
____ was originally an anti-epileptic drug
-Gabapentin
What does Gabapentin do as far as analgesia goes?
-Interacts w/ specific subtype of Ca+ channel complex (alpha-2-delta subunit) & decreases the expression of this subunit
-(helps direct amplified nervous system to a de-amplified nervous system)
What is a downside of using Gabapentin?
-It can cause some sedative effects
T/F: Gabapentin can be used for acute pain
FALSE!
-Gabapentin’s effect requires pain already be in an amplified state, & changing the receptor subtypes is a low process, so Gabapentin should be used for established pain
What is important to note about gabapentin dosing?
-In general, animals are very tolerant of even high doses
-In anesthesia, go for formulated drugs and save the higher doses for when you want to escalate the dose
What is “NMDA”?
N-Methyl D-Asparate
-Related to gabapentin (called Pre-gablin)
How does the NMDA receptor work?
-Becomes activated by recurrent depolarization -> loss of Mg plug
-When activated, massively amplifies Ca release & thus nerve transmission
_____ is a massive contributor to neuro-inflammation
-NMDA
What are excellent drug targts of NMDA?
-Ketamine
-Amantadine (most common orally used)
-Methadone
-+/- Tramadol (minor)
There is less ataxia associated with _____ than Gabapentin, so often used in place of Gabapentin in patients who can’t use that drug.
Pre-gablin
What are the NMDA antagonists?
-Amantadine
-Memantine
What do NMDA antagonists do?
-Antagonize central sensitization, glial activation, and decrease opioid tolerance, making a number of drugs more effective
-May also be neuroprotective, and some evidence for using them to decrease rate of neuro-degenration in chronic conditions, even if non-painful (Degenerative myelopathy)
There are so many side effects for Amantadine, should we stop using this drug?
-A lot of the side effects are from the human side from a whole different disease
-She has not really seen many side effects in her practice
____ is highly correlated with pain
Obesity
_____ = pro-inflammatory
Fat (obesity)
Weight reduction = _______
Analgesic
What has a greater impact in veterinary studies than even putting dogs on NSAIDs?
-Simply losing weight
In addition to controlling obesity, what else can reduce inflammation?
Diet:
-Fresh foods vs highly preserved foods (reduced carbohydrates, processed meats)
-Foods high in anti-oxidants (fish, fruit & vegetables, supplements)
What is the problem with supplements?
-Lots of supplements are out there but none have the same amount of data available as drugs (so more buyer beware)
What are the research challenges for supplements?
-Pressure from public & professionals for more information
-Pharmacokinetic studies require identifying active compound
-Current studies are primarily low-quality, clinical response studies
What is a supplement we can be pretty confident about because it is an FDA approve injectable drug in dogs?
-Adequan
What do we classically use Adequan for in canines and why?
Non-infectious arthritis
-Decreased catabolic enzymes
-Enhance anabolic enzymes
Significantly improves ROM & orthopedic score compared w/ placebo at 5 weeks
What do we need to do after doing an intra-articular treatment for OA?
-Get them into therapy
-Get them into a regular fitness and weight-loss program
(Do this so we don’t have to go back in and re-inject those joints)
____ is a temporary measure to improve a patient with OA’s overall metabolic health
Injecting joints
What is regenerative therapy?
-Injection of small volumes of biologically active substances into joints & soft tissues (promote tissue repair & growth, reduce pain)
-Augment natural healing process
When would we use regenerative therapy?
-Osteoarthritis (refractory to medical management, acute flair/breakthrough, undergoing sx)
-Perioperative (articular fracture repair, post arthroscopy)
-Postoperative (Slow return to function)
What is SynovetinOA?
-Product that uses radiation therapy into joints to break down the neutrophil population (only has to be done once a year)
-Breaks the vicious cycle of inflammation & chronic pain
What is the problem with using SynovectinOA?
-Clinic has to have a permit for radiation therapy already or it is not very practical to use this
What are anti-NG monoclonal antibodies?
-Pain sensation neurotransmitters can induce peripheral inflammation at the site of nociceptors after anti-dromal axoplasmatic transport
-May induce release of synovial fluid w/ neurologic inflammation
What does anti-NG stand for in anti-NG monoclonal antibodies?
-Anti-nerve growth factor
What are some examples of Anti-NG monoclonal antibodies?
-Solensia
-Librela
Wait, aren’t people saying solensia and librela are bad?
-Not necessarily
-A lot of patients w/ chronic OA pain as they age neurologic deficiets as well, so those patients may experience worse neurological symptoms on those drugs
-However, can stop the drug and the animals usually go back to normal
What does “non-pharma” mean?
-Physical medicine
What is physical medicine?
-Has a physiological basis (like drugs do)
-Modalities that use mechanical, thermal or electrical forces endogenous to physiology of living organisms
What can physical medicine do?
-Directed therapies are shown to alter distensible tissues, nerves, neurotransmitters, genetic transcription, cellular metabolism, & other biochemical substrates
What are examples of physical medicine?
-Thermal therapies
-Tissue deformation
-Laser
-Biologicals
-Exercise/physical rehabilitation
-Shock wave therapy
-Hyperbaric oxygen therapy
-Electrical & magnetic field therapies
What is Integrative medicine?
Integration of homeostatic neurotransmitter systems:
-Opioidergic
-Serotonergic
-Noradrenergic
-Endocannabinoid
What species excels at auto-regulation?
-Cats
What is an integral part of chronic pain management?
Calibration of the pet owner
-Vital source of information
-Vital source of therapy
What falls under the “pharmacologic” mechanism of physical medicine modalities?
-How temperature related modalities work
-Tissue deformation (how fascia are associated with disease, modalities that interact with fascia)
-Neuromodulator
-Cartilage health & joint mobility
What can we do to help with tissue deformation?
-Acupuncture
-Massage
-Manual therapy
-Stretching
-Exercise
There is a powerful modulator of in intrinsic healing in
soft tissues
What happens when the connective tissue complex is deformed?
-Growth factors and a variety of proteins and neurotransmitters are released
Fibroblasts in loose connective tissue respond to _____ within minutes by _____
Stretching within minutes by increasing ATP & enhancing cytoskeletal relationships w/ neighboring cells
What can stretching the back do?
-Improve gait, mechanical sensitivity & connective tissue inflammation in a rodent model
Viscoelastic changes in ____ can happen fairly quickly
Fascia
What happens if you stretch beyond the limits?
-You will rip the tissue
There are ______ effects of physical medicine modalities
Hypoalgesic
How can motion be pain management?
-Movement is essential for body function
-Motion can be internally applied or externally applied
-Aerobic exercise improves outcomes for variety of conditions
-Modest voluntary exercise reduces pain & stress related outcomes
_______ type exercise provides greater analgesia than strength-type training
Isotonic and balance type exercise
What is the use of a therapeutic laser?
-Photons of light energy penetrate tissue & stimulate chromophores in the mitochondria
-Biphasic dose response (low doses may stimulate healing while higher doses appear to inhibit)
What does therapeutic laser do?
-Increases oxidative phosphorylation of ATP
-Alter cellular membrane permeability
-Increase growth factors & tissue repair
-Increase blood-flow
-Reduce pain signaling through opioids, nerve conduction alteration & immune modulation
What are the direct healing medical effects of electricity?
-Direct current stimulation enhances bone & nerve repair mechanisms at low intensity, but are destructive at high intensity
-PEMF: pulsed electrical magnetic field therapy
What types of electricity are there and what are there effects?
Chemical
-Receptor mediated effects
Mechanical
-Mechanotransduction
Thermal
-Increase local blood flow
What are the important promoters of De-Amplifying Neuromodulation?
-Acupuncture
-Motion, Physiotherapy, Rehabilitation
-Vagal nerve stimulation
-System Modifying Pharmacology (anti-inflammatories, Gabapentin/Pregablin, Cannabinoids, NMDA antagonists, Pain vacations)
_____ nerve is very important as a pain signaling pathway
Vagus nerve
How can we modulate fascia?
-Acupuncture
-Stretching
-Massage/tough
-Pressure waves (tapping, vibration, shock wave therapy)
