7.14 (13.2) Cancer induced bone pain Flashcards
List the three most common sites of metastatic disease
- lung
- liver
- bone
List the two types of nerves that carry nociceptive information
a-delta and c fibres
List the three predominant types of stimuli that result in nociception
- mechanical
- thermal
- chemical
Where do nociception carrying neurons synapse?
Provide 4 examples of neurotransmitters that modulate second order neurons at the level of the spinal cord
Laminae I and II in the superficial dorsal horn of spinal cord
NTs - glutamate, GABA, glycine
FS: glutamate, GABA, opioid, substance P, serotonin (GGOSS)
Where do the ascending noiceptive spinal tracts cross over? What tract do these nerves travel in? Where do they synapse?
They crossover after synapsing in the spinal cord (anterior white commissure) –> travel superiorly in spinothalamic tract –> synapse in thalamus
FS:
Second order neurons cross at the anterior white commissure
List three factors that interact to create the experience of cancer induced bone pain (CIBP)
- tumor type
- malignancy site
- degree of bony destruction*
- local changes in sensory nerves*
- inflammation*
- bone microenvironment
List 2 higher brain areas that act as the origins of descending pathways to modulate nociception at the level of the spinal cord
Nucleus raphe magnus (medulla)
Rostral ventromedial medulla
Fs: Nu Ra Ma - RUM… sorry this is so bad
What is the proposed role of osteoprotegrin (OPG) in the pathology of cancer induced bone pain
OPG acts by sequestering RANKL, preventing osteoclast activation and reducing bone resorption
This feedback loop is disrupted in CIBP, with a marked osteoblastic inflammatory response, increased secretion of a range of cytokines increasing osteoclast activity, and an increased ratio of RANKL to OPG
FS:
- RANKL binds to RANK which activates osteoclasts
- OPG binds to RANKL so that it can’t bind to RANK
- PTHrp (cancer) increases osteoblastic inflammatory response = RANKL > OPG —-> osteoclast activation —-> bone resorption
FS: denosumab mimics OPG
How does gabapentin work to reduce CIBP
It reduces activity of dorsal horn neuron wide dynamic range (WDR) neurons.
WDR neurons appear to alter in CIBP, with increased responsiveness to mechanical and thermal stimuli in addition to ongoing spontaneous activity
CIBP treatments
Medication - list 4
Cancer treatment - list 2
Intervention - list 4
XRT, radioisotopes, hemibody XRT
TENS
complementary tx (acupuncture)
bisphosphonates
surgery
anesthetic interventions (they put vertebroplasty here)
PT, OT
WHO analgesic ladder
topical tx (lidocaine)
tumoricidal agents
new emerging tx (gabapentin and other glumate inhibitors
)
5th Ed. Figure 13.2.3
FS:
Medications
- opioids
- steroid
- nsaids
- bisphosphonate
- gabapentin
- topical
Cancer treatment
- radiation
- systemic treatment
Interventions
- Kyphoplasty
- Surgery
- PT/OT
- TENS
List 3 characteristics of pain associated with CIBP
tonic background pain
spontaneous pain at rest
movement-related pain
incident pain (related to event other than movement)
What are the three most common sites of bone mets
vertebral
Chest wall
pelvis and long bones
What is the most common individual site of bone mets with the following malignancies:
- head and neck
- breast
- lung
- upper GI
- lower GI
- prostate
head and neck - skull
breast - vertebral (!!!)
lung - chest wall
upper GI - vertebral (!!!)
lower GI - pelvis / long bones
prostate - pelvis/ long bones
What is the most common type of pain syndrome seen in breast, prostate and hematlogic ca
generalized bone pain
List two consequences of breakthrough pain in CIBP
increased anxiety and depression
greater functional impairment
List five symptoms of opioid toxicity
hallucinations
confusion
agitation
sleepiness
poor concentration
vivid dreams
hyperalgesia
FS: allodynia, hyperalgesia, myoclonus, delirium, seizure (OIN)
What is the gold standard treatment for CIBP?
radiotherapy
What are three strategies for treating breakthrough pain in CIBP?
treat underlying cause of pain
optimizing around the clock analgesia
Specific pharm or non-pharm interventions for BT pain
List three mechanisms through which bisphosphonates treat CIBP
inhibit the differentiation of stem cells into osteoclasts*
cause apoptosis of osteoclasts*
affect interaction between osteoclasts and blasts via OPG RANKL and RANKL axis
inhibit growth of some tumor cells
stimulate immune system against tumor
cause apoptosis of tumor cells
delay development of skeletal events*
FS: bisphosphonate increase bone density by interfering with osteoclasts:
- affect interaction of osteoclast and blast via RANKL (produced by osteoblast) RANK axis
- prevent osteoclast differentiation
- cause osteoclast apoptosis
List three side effects of bisphosphonates
flu like syndrome
injection site reaction
renal toxicity*
osteonecrosis of the jaw*
Hypocalcemia*
List three risk factors for osteonecrosis of the jaw in the setting of bisphosphonate use
dental extraction
local trauma
local infection
systemic chemo
FS:
Poor dental health
Gingivitis
Dental procedure
Poor healing (chemo, radiation, steroid)
What is the most common radiation modality used for CIBP? What two other mechanisms can be used
external beam XRT , local field - most common
wide field XRT
radioisotope treatment (internal, can be PO or IV)
List four pathology-related factors that are taken into account when deciding if an impending pathological fracture should be operated on
Lesion:
- size and involvement (maximum amount of cortex destroyed)
- location
- type: blastic, lytic, combo
degree of pain
What are two complications that can occur in cementoplasty
cement leak that can cause chemical damage in epidural space and cord/nerve root compression
cement embolization
Briefly describe the pathophys of met bone pain in relation to osteoclast activation.
◆ Tumour cells stimulate osteoclast activation through a series of cytokine mechanisms
◆ in doing so promote bone damage which leads to a compensatory but often inefficient osteoblast response.
FS:
Cancer release PTHrp -> osteoblast to release RANKL-> bind to RANK and activate osteoclast -> bone resorption
Role of denosumab
What is the main effect re bone?
How does it compare to pamidronate and ZA?
◆ Denosumab is a monoclonal antibody which targets and inhibits RANKL***
◆ main effect is delay onset of pain (vs analgesia) (!!!)
◆ was associated with a statistically sig improvement vs placebo for:
- time to first on-study skeletal-related event
- risk of first and subsequent skeletal-related events
- skeletal morbidity rate (RR 0.47, 95% CI 0.25–0.67)
◆ superior to pamidronate & zoledronic acid in time to fisrt skeletal-related event
Name THREE fracture assessment from met disease tools.*
◆ Mirels’ Score
◆ Dutch Bone Metastasis study
◆ CT structural rigidity analysis
◆ Spinal Instability Neoplastic Score (SINS)
Solitary or oligo-bone mets are most commonly seen in which malignancies?
◆ Prostate
◆ Breast
