Chronic Nonmalignant Pain Treatment

allodynia

painful response to a non-noxious stimulus (ex. rubbed by a feather)

nonspecific analgesic options for low back pain

likely that a single agent won't help 1. NSAIDs 2. opioids 3. "muscle relaxants" 4. analgesic antidepressants (TCAs, SNRIs, others) 5. alpha-2 adrenergic agonists (tizanidine) 6. topical LA (local anesthetic)

acute to chronic continuum (sensitization - acute state)

local injury in some patients leads to chronic, intractable pain - in the acute state ... 1. primary NT is *glutamate* which is released and activates channels 2. *AMPA-mediated Na-K channels* are *activated* allowing Na entry with K efflux 3. K then negatively feeds back to stabilize the nociceptor membrane, thereby decreasing glutamate discharge 4. although receptive to glutamate, the *NMDA-mediated channels* remain relatively *inactive* (plugged by Mg)

acute to chronic continuum (sensitization - chronic state)

local injury in some patients leads to chronic, intractable pain - in the chronic state ... 1. pronounced glutamate input can occur 2. a transformation in which the *Mg plug is lost* and *NMDA channels* are then *activated* 3. this leads to a formation of the signal from a predominantly *Na-K flux to a Ca flux* 4. leads to *increased intracellular Ca* which via protein kinase C activation, *leads to increased nitric oxide* 5. *nitric oxide* then diffuses out of the dorsal root to the nociceptor terminal where it *shuts off the K channels* via activation of guanyl synthase, leading to an *interruption of the normal negative feedback loop*

___ and ___ functions become dysfunctional in neuropathic pain

modulation and transmission

conclusion

1. CNMP is a difficult, common medical problem 2. treatment is complex and multimodal 3. pharmacotherapy approaches are complex and use medications alone and in combination 4. off-label drug prescribing is common 5. screen and assess patients for pain complaints 6. monitor and document findings to protect the patient, society, and medical and pharmacy clinicians 7. modify to decrease pain symptom and associated morbidity

what are complex regional pain syndromes or Reflux Sympathetic Dystrophy (RSD)?

1. Type 1 = noxious event to tissues, like trauma 2. Type 2 = peripheral nerve/root injury, brachial plexus 3. sympathetic nervous system also damaged

agents to treat neuropathic low back pain

1. all nonspecific drugs (NSAIDs, opioids, muscle relaxants, analgesic antidepressants, alpha-2 adrenergic agonists, topical LA) 2. AEDs 3. others

neuropathic pain sensations

1. allodynia 2. hyperalgesia 3. burning (like foot on a hot plate) 4. tingling 5. electrical shock, shooting 6. closest example of "hitting your funny bone" 7. disability is high because of pain symptoms

TCA contraindications

1. anticholinergic property is what we're thinking about here 2. elderly = cognitive functional impairment, sedative 3. older guys = BPH

tramadol/tapentadol MOA

1. central analgesic 2. MOA - weak mu-receptor agonist and weak NE and SE reuptake inhibition 3. synergy between mechanisms 4. useful in neuropathic pain

botulinum toxins use in pain

1. demonstrated efficacy in - myoclonus, tension-type headache, trigger points, myofascial pain, back pain, cervical dystonia and other focal dystonias, and spastic disease states 2. usually reserved for refractory cases

generalized (poly) painful peripheral neuropathies

1. diabetes 2. alcohol/toxins/drugs 3. HIV 4. amyloidosis 5. Vit B deficiency 6. hypothyroidism

focal/multifocal painful peripheral neuropathies

1. entrapment 2. phantom limb/stump 3. post-trauma 4. post-herpetic 5. diabetic 6. ischemic

injection therapies for low back pain

1. epidural steroid injections 2. facet steroid injections 3. botulinum toxin injections

standard assessment protocol required

1. have patient describe their pain through structured interview - how does it affect daily living? 2. physical examination and history 3. supportive tests, labs, radiology, nerve conduction 4. psychological and social assessment 5. rule out treatable causes of pain, establish diagnosis 6. begin pharmacotherapy protocols based on symptoms 7. substance abuse history 8. medication history

interventional treatment options for low back pain

1. injection therapies 2. neural blockade 3. implant therapies

opioid dependence risk with long-term opioid use after back injury is great and results in ...

1. longer disability (29 vs 17mo) 2. 2.5x more likely to have surgery 3. 2.5x more likely to have antisocial disorder 4. 2x more likely to have and had pre-injury substance use disorder 5. 90% still have moderate to severe pain

skeletal muscle relaxants are beneficial for pain states involving ..., they work by interrupting ...

1. muscle spasm 2. pain-spasm-pain cycle

American Academy of Pain consensus statement on opioids for CNMP

1. must alleviate under-treated pain and suffering 2. places much greater emphasis on thorough patient assessments and frequent evaluations, creating treatment plans and documenting effects 3. individualized treatment plans 4. written agreements (contracts) with patients 5. functional improvement outcomes must be overall goal

general approach to pharmacologic treatment of neuropathic pain

1. neuropathic pain is not easily treated with conventional analgesics and requires a multimodal approach 2. there can be a nociceptive component 3. most effective agents affect nerve transmission

botulinum toxins MOA

1. neurotoxins block acetylcholine release at neuromuscular synapses, causing paralysis 2. may also have independent analgesic effects - anti-inflammatory, blocking release of glutamate, reducing concentrations of substance P

opioid usage for neuropathic pain

1. opioids can be adjuncts but must be used at much higher doses than nociceptive pain 2. big risks for little benefit in general

general considerations for chronic pain treatment

1. oral conservative therapy is first line 2. titrate upward for trials with each medication 3. additional medications may be added 4. general outlines "work" for back, diabetic, and other neuralgias 5. herpetic neuralgia responds to topical capsaicin and lidocaine patch 6. multimodal therapy may advance to IT delivery with opiates, clonidine, ziconotide

other commercially-available treatments for neuropathic pain

1. other AEDs (antiepileptic drugs) = topiramate, oxcarbazepine, levetiracetam, zonisamide, tiagabine 2. other ADs (antidepressants) = SNRI (venlafaxine), SSRI (paroxetine, citalopram), others (maprotiline, bupropion) 3. alpha-2 adrenergic agonists (tizanidine, clonidine) 4. NMDA antagonists (ketamine, memantine) 5. other Na-channel blockers (mexiletine, tocainide, flecainide) 6. cannabinoids (THC, nabilone)

impact of chronic pain on the dimensions of quality of life include ...

1. physical - functional ability, strength/fatigue, sleep and rest, etc. 2. social - caregiver burden, roles and relationships, affections/sexual function, etc. 3. psychological - anxiety, depression, enjoyment/leisure, happiness, etc. 4. spiritual - suffering, meaning of pain, etc.

nonpharmacologic treatment options for low back pain

1. physical medicine approaches (physical therapy, exercise, and weight control) 2. psychological approaches 3. lifestyle changes

simplistic algorithm for peripheral neuropathic pain

1. postherpetic neuralgia and focal nueropathy? yes --> lidocaine patch or capsaicin cream; no --> go to 2 2. TCA contraindication? yes --> gabapentin/pregabalin no --> TCA (SNRI) 3. if not solved, try the other option (gabapentin -> TCA (if no TCA contraindication), TCA -> gabapentin) 4. if TCA contraindications and gabapentin/pregabalin doesn't work --> tramadol, oxycodone

why are dependence-producing agents used with caution for chronic pain

1. potential for abuse is great 2. patients use as a shortcut to controlled physical activities 3. detoxification may be necessary at some point to achieve optimal analgesia - well-defined, short-term therapy is essential

skeletal muscle relaxants improve ___, help patients regain ___, and facilitate ...

1. range of motion 2. function 3. rehab and therapeutic exercise

medications used with neuropathic low back pain

1. responsive to neuromodulators 2. may require polypharmacotherapy

lesions of CNS include

1. spinal cord injury 2. brain infarction (thalamus and brainstem) 3. spinal infarction 4. multiple sclerosis

implant therapies for low back pain

1. spinal cord stimulators 2. neuraxial infusion

symptom = electrical shooting pain with flinching with fasciculation of muscle (moving on its own) target = ? medication options = ?

1. target = maybe Ca channel 2. MOA = Ca channel antagonist 3. option = this is underlying mechanism of antiepileptic drugs --> gabapentin may be a choice

corticosteroid ADRs? length of therapy?

1. variety of adverse effects from systemic administration (cause demineralization) 2. should be limited to 1-2 weeks of therapy

reassessment considerations

1. was the medication successful in reducing any pain or to some meaningful degree? 2. do they feel better or worse? 3. can they do more than they used to? 4. document the improvement 5. discontinue if no benefit!!! 6. too many patients on cocktail 7. add another medication for a trial and repeat

chronic neuropathic pain syndrome results from ...

continuous abnormal processing of sensory input and subsequent physiologic (plasticity) changes within the nervous system

central sensitization, once established, requires ...

larger doses of analgesics to suppress pain

antianxiety agents in neuropathic pain

BZDs (alprazolam, diazepam, etc.) also used as anticonvulsants and antispasmodics

symptom = spontaneous shooting pain medication options = ?

TCAs, topical lidocaine

nociceptive low back pain is responsive to ...

analgesics

cause of nociceptive low back pain

caused by activity in neural pathways in response to stimuli potentially damaging to tissue

cause of mixed (nociceptive/neuropathic) low back pain

caused by both primary injury and secondary effects

what kind of pain is seen in chronic pain?

chronic non-malignant pain can have either nociceptive or neuropathic pain or both

adverse effects of antianxiety agents (BZDs)

cognitive impairment, physical dependence, worsen depression, additive CNS depressant effects when combined with opioid

first line use for breakthrough CNP episodes?

dependence-producing agents --> replace with non-narcotic as soon as possible

tramadol/tapentadol ADRs

dizziness, vertigo, GI, headache

skeletal muscle relaxant ADRs

drowsiness, dizziness, light-headedness, fatigue, sedation

general approach to pharmacologic treatment of nociceptive pain (acute pain)

easy to treat with conventional pharmacologic agents

symptom = spontaneous shooting pain pathology process = ?

ectopic nerve impulse

hyperalgesia

exaggerated painful perception to normally noxious stimulus (like a pin-prick)

T/F - chronic pain is acute pain that persists

false

dependence-producing agents for chronic pain

for chronic therapy use ... 1. SR opioids or 2. methadone (since it has dual action at NMDA receptor)

goal of therapy in chronic pain?

improve daily function and quality of life (very uncommon that we can remove pain)

antianxiety agents in chronic pain

in chronic pain, BZDs (alprazolam, diazepam, etc.) can relieve pain by reducing anxiety associated with the chronic pain state and resulting insomnia and muscle tension

skeletal muscle relaxant agents

include - baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, diazepam, metaxalone, methocarbamol, orphenadrine, tizanidine

cause of neuropathic low back pain

initiated or caused by primary lesion or dysfunction in the nervous system

which type of chronic pain is most common?

neuropathic pain is more common problem

should chronic pain be treated with acute pain models?

no - results in poor outcomes

prolonged bed rest to treat low back pain?

no significant scientific merit

what type of pain seen with low back pain?

nociceptive, neuropathic, both (most cases are mixed etiology)

treatment of mixed (nociceptive/neuropathic) low back pain may require ...

poly-pharmacotherapy

corticosteroids general MOA

powerful anti-inflammatory agents that reduce nociception

what may prevent central sensitization or progression from acute toward chronic pain?

preemptive balanced analgesia, or interruption at multiple points in the pain pathway

omnibus goal of chronic nonmalignant pain treatment

promote optimal functional of living

neural blockade for low back pain

radiofrequency median branch block

avoid use of tramadol/tapentadol in ...

seizure risk patients

symptom = spontaneous shooting pain MOA of drug to target symptom = ?

selective sodium channel drug

symptom = spontaneous shooting pain targets = ?

sodium channel

post-injury afferent nerve changes

some nerves degenerate and the lesions trigger ... 1. expression of Na+ channels on damaged C-fibers 2. expression of Na+, α-adrenoceptor on uninjured fibers 3. promotes hyperexcitation and spontaneous nerve firing (more channels for Na and adrenal receptors = more sensitive)

basic summation of sensitization

spinal cord changes because getting all these signals and confuses it

tramadol/tapentadol dosing strategy

start low and increase dose to tolerance

neuropathic pain originates from ...

stimulation and damage to afferent nociceptive nerve fibers, not the receptors

the terrible triad of chronic pain ...

suffering, sleeplessness, sadness

first line pharmacotherapy for neuropathic pain

supported by good evidence 1. alpha-2-delta nerve modulators = gabapentin and pregabalin 2. antidepressants - TCAs and duloxetine 3. carbamazepine for TN (trigeminal neuralgia) 4. lidocaine patch 5% 5. opioid analgesics, including tramadol

corticosteroid injections are widely used for ...

tendonitis, bursitis, tenosynovitis, epicondylitis

topical product usage in neuropathic pain

topical products such as lidocaine and capsaicin for certain focal neuropathy

drugs of choice for neuropathic pain

tricyclic antidepressants (such as amitriptyline) or anti-epileptic drugs (such as gabapentin or pregabalin)

corticosteroids are often used for what type of pain?

tumor-related pain