The Pain of COVID-19: Treatment of Chronic Pain During the COVID-19 Pandemic Faculty presenters for this session include: Bennet Davis, MD; Pain Program Director, Sierra Tucson Amy Kennedy, PharmD, BCACP; Clinical Assistant Professor, University of Arizona College Pharmacy; Clinical Pharmacist, El Rio Health Kathy Davis, RN, BSN, ANP-C; Nurse Practitioner, El Rio Health Pain Program September 2, 2020

1. The Pain of COVID-19
Treating Chronic Pain During the COVID-19
Pandemic
September 2, 2020

2. CME Credit
• Bridgeport Hospital Yale New Haven Health is accredited by the Connecticut State
Medical Society to sponsor continuing medical education for physicians. The
Bridgeport Hospital Yale New Haven Health designates this live activity for a
maximum of one (1) AMA PRA Category 1 CreditsTM. Physicians should claim only
credits commensurate with the extent of their participation in the various
activities.
• This activity has been planned and implemented in accordance with the Essential
Areas and policies of the Accreditation Council for Continuing Medical Education
through the joint sponsorship of Bridgeport Hospital Yale New Haven Health and
the Weitzman Institute. Bridgeport Hospital Yale New Haven Health is accredited
by the Connecticut State Medical Society to provide continuing medical education
for physicians.
• The content of this activity is not related to products or services of an ACCME-
defined commercial interest; therefore, no one in control of content has a relevant
financial relationship to disclose and there is no potential for conflicts of interest.
2

3. Managing Chronic Pain During Covid-19

4. 6,073,121 cases on 9/1/20 up from 5,746,940 cases on 8/25/20 184,644 deaths
https://coronavirus.jhu.edu/map.html
COVID-19 in the United States

5. Average daily cases in the last week

7. COVID-19 News updates
• Plasma?
– Emergency Use Authorization - Food and Drug
Administration
• Aug. 23
– There are currently no data from well controlled,
adequately powered randomized clinical trials that
demonstrate the efficacy and safety of
convalescent plasma for the treatment of COVID-
19 - NIH

8. COVID-19 News updates
• New York City is delaying the start of the
school year by 10 days
• Other schools with problems:
– University of South Carolina – suspended students
• World:
– Indonesia: 100+ and 70 nurses died COVID-19
– Russia passed 1 million cases
• #4 in the world

9. Resources
• Nuvance health 1000+ articles reviewed:
https://spark.adobe.com/page/qrH7iY0Gi0hU9/
• CDC:
https://www.cdc.gov/coronavirus/2019-ncov/index.html
https://emergency.cdc.gov/coca/calls/2020/
• WHO:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019
• Johns Hopkins:
https://coronavirus.jhu.edu/map.html
• Others
https://www.thelancet.com/coronavirus
https://covidactnow.org/

10. The Pain of COVID-19
Treating Chronic Pain During the COVID-
19 Pandemic
Bennet Davis, M.D.
Kathy Davis, ANP-C
Amy Kennedy, PharmD

12. What is Pain?
• Nociceptive pain
• Neuropathic pain from physical
nerve damage or disease
• Neuropathic pain from a Threat
Adapted Nervous System
(Nociplastic pain)
• “Emotional” Pain: Grief,
Rejection, Isolation
An experience produced
by any combination of:

13. What is Pain?
“Pain that arises from altered
nociception despite no clear
evidence of actual or
threatened tissue damage
causing the activation of
peripheral nociceptors or
evidence for disease or lesion
of the somatosensory system
causing the pain.”
Nociplastic Pain:
https://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698#Nociplasticpain
International Association for the Study of Pain. 2017

14. What is Pain?
• Culture, Beliefs, Values,
Assumptions
• Anxiety, depression
An experience produced
by any combination of
the 4 processes,
interpreted through the
lens of the individual’s
life experience and
emotional state:

15. What is Pain?
• Family
• Work
• Codependent
relationships
An experience produced
by any combination of
the 4 processes, felt and
interpreted through the
lens of the individual’s
life experience and
emotional state, and
modified by the
important relationships
in the individuals life

17. The two brain pain circuits

18. Kross E. Proceedings of the National Academy of Sciences. 2011;108 (15): 6270-6275
Author’s conclusion: “These results give new meaning to the idea
that social rejection ‘hurts.’”

19. Social interactions mediate pain perception
1. Socially isolated people have a lower pain threshold
2. Degree of social support at diagnosis of RA predicts
pain intensity at 3 year follow up
3. Pain scores correlate positively with perceived
social support in people with chronic
musculoskeletal pain
1. Eisenberg N. Pain 2006;126:132-8
2. Evers A. Beh Res Ther. 2003;41:1295-1310
3. Hsu. Clin J Pain 2014;30:713-23

20. Our study provides evidence that the impact
of pain is reduced in individuals who perceive
a greater sense of inclusion from and
engagement with others.
The Impact of Social Isolation on Pain
Interference (PROMIS® pain measures): A
Longitudinal Study
Karayannis N. Annals of Behavioral Medicine. 2019; 53: 65-74

21. Acetaminophen Reduces Social Pain: Behavioral and
Neural Evidence
Dewall C. Pschol. Sci. 2010 Jul;21(7):931-7
•. 2010 Jul;21(7):931-7
In two experiments, participants took acetaminophen or
placebo daily for 3 weeks. Doses of acetaminophen reduced
reports of social pain on a daily basis (Experiment 1). We used
functional magnetic resonance imaging to measure
participants' brain activity (Experiment 2), and found that
acetaminophen reduced neural responses to social rejection in
brain regions previously associated with distress caused by
social pain and the affective component of physical pain (dorsal
anterior cingulate cortex, anterior insula)

22. We used a Mu opioid receptor (MOR) radiotracer to
measure changes in MOR binding potential (that is, in
vivo receptor availability) with positron emission
tomography during social feedback.
We found that social rejection as well as acceptance
activated the MOR system above baseline in different brain
regions, showing that the endogenous opioid system
responds to social feedback in humans.
Activation levels extracted from the left amygdala were
positively correlated with the personality trait resiliency,
suggesting that during rejection high-resilient individuals
are more capable of MOR activation, which may be
protective or adaptive.
Hsu D. Molecular Psychiatry 2013: 18: 1147
Endogenous opioid mediates response to social rejection
And improves resilience to social rejection and isolation

23. Variation in the μ-opioid receptor gene (OPRM1) is associated
with dispositional and neural sensitivity to social rejection
Participants (n = 122) completed a self-report inventory of dispositional
sensitivity to social rejection and a subsample (n = 31) completed a
functional MRI session in which they were rejected from an online ball-
tossing game played with two supposed others. The A118G
polymorphism was associated with dispositional sensitivity to rejection
in the entire sample and in the fMRI subsample. Consistent with these
results, G allele carriers showed greater reactivity to social
rejection in neural regions previously shown to be involved in
processing social pain as well as the unpleasantness of physical
pain
PNAS September 1, 2009 106 (35) 15079-15084

24. Chronic pain and COVID 19
• Social isolation directly increases pain
• Social isolation increases anxiety and depression
• Social isolation increases fatigue
• The endogenous opioid system is involved in
regulating response to isolation
• Some people have a variant of the opioid receptor
that makes them more vulnerable to the effects of
isolation

25. Chronic pain and COVID 19
• Cognitive barriers worsened by COVID and isolation
– Fear avoidance
– Feeling misunderstood
– Worry about keeping up
– Somatization
• COVID 19 interferes with access to care and self care
– Transportation challenges
– Financial challenges
– Gyms and pools closed
– Alternative medicine closed
– Elective procedures and surgeries closed

26. 1. Opioid prescribing has increased
20% since Jan 2020
2. Overdose rates on fentanyl have
increased since Jan 2020

27. At risk populations
– Prescribed opioid for pain – risk of withdrawal
– Using opioid to some degree as a psychotropic
– Decreased social resources
– Low financial resources
– Transportation challenged
– IT challenged
– Geographically remote communities

28. What to do??
• Connection to others via electronics
• Support groups
• Hobbies
• Pets
• Self care
– Diet
– Exercise
– Sleep
– Meditation
– Meter the news
• Treat anxiety and depression
• Recognize and treat trauma
• Ease roadblocks to care
• Level the tech playing field

29. Support groups to counter isolation
• American Chronic Pain Association
https://www.theacpa.org/about-us/support-groups/
• The Mighty https://themighty.com/topic/chronic-pain/
• The National Fibromyalgia and Chronic Pain Association
https://www.fibroandpain.org/chronic-pain/chronic-pain-
support-community
• My Chronic Pain Team
https://www.mychronicpainteam.com/users/sign_in
• NAMI https://www.nami.org/Support-Education/Mental-
Health-Education/NAMI-Peer-to-Peer

30. Prescribing opioids during COVID 19
Kathy Davis, ANP-C

31. COVID 19 OPIOID PRESCRIBING CHALLENGES
TELEHEALTH
• Telehealth visits – the new norm.
– Keep Phone visits at a minimum vs. Virtual visits
– Many possible technological interruptions during
telehealth visits. Loss of focus, wastes valuable visit
time.
– Lack of privacy
• Is it Ok to see a patient for the first visit via
telemedicine?

32. COVID 19 OPIOID PRESCRIBING CHALLENGES
Non-Opioids TREATMENTS
– Patients find it difficult to follow through on chronic pain treatments
due to COVID restrictions and fears.
Examples: physical therapy, massage, acupuncture, referrals for
interventional treatments, going to radiology for necessary films,
going to group classes for exercise and weight loss programs, etc.
– Not going to gyms. Some getting home equipment.
– On line classes at our CHC, You Tube, Webinars, and Podcasts all
available.

33. COVID 19 OPIOID PRESCRIBING CHALLENGES
MONITORING
Monitoring of patients on opioids
• Toxicology screening, signing opioid agreement, completing
mood and pain interference screening documents, etc.
• Randomly bring patients in for in clinic visit so can get a UDS
and sign opioid agreement.
• Use risk stratification tools to determine frequency of UDS:
ORT (opioid risk tool) or SOAPP-R
• Document reasons for exceptions.

34. COVID 19 OPIOID PRESCRIBING CHALLENGES
DOSAGE CHANGES
• This is not the time to make major changes in opioid dosing up
or down unless for safety reasons
• Decreases and delays in elective surgery and procedures may
cause the need to support with opioid longer or delay lowering
dose plans
• If need to wean, recommend these guidelines: Davis B, Archambault C, Davis
K, et al. A Patient –Centered Approach to Tapering Opioids. VOL 68, NO 10 | DECEMBER 2019 | THE
JOURNAL OF FAMILY PRACTICE

35. COVID 19 OPIOID PRESCRIBING CHALLENGES
BEHAVIORAL HEALTH CONCERNS
• Social isolation is increasing pain and mood disturbance, negatively
impacting self-care.
• Increased financial strain, Increased risk of diversion, more
homelessness, high stress levels everywhere.
• BH treatments may be on hold
• What to do? Focus on the highest risk patients
• Implement screening tools when come in, GAD 7, PHQ9, PROMIS
pain interference and intensity, ACE and PCL-5 Initiate BH support.

37. Pharmacist perspective on pain
in COVID-19
Amy K. Kennedy, PharmD, BCACP
2020

38. Factors worsening adherence
• Impact on social interaction/mental health
• Financial
• Avoidance of care
• Medication shortages and contamination
• Changing pharmacy landscape

39. BRAIN
Pharmacologic Agents Affect Pain Differently
Descending Modulation
Central Sensitization
PNS
Local Anesthetics
Topical Analgesics
Anticonvulsants
Tricyclic Antidepressants
Opioids
Anticonvulsants
Opioids
NMDA-Receptor Antagonists
Tricyclic/SNRI Antidepressants
Anticonvulsants
Opioids
Tricyclic/SNRI Antidepressants
CNS
Spinal
Cord
Peripheral
Sensitization
Dorsal
Horn

40. SSRI antidepressants
• citalopram (Celexa)
– Few drug-drug interactions (DDIs)
– High serotonin specificity
– Typical or less SSRI side effects
– 10-40 mg/day (hepatic impairment consider 20 mg/day)
• escitalopram (Lexapro) – no generic available
– Simple dosing (10-20 mg/day)
– “S” molecule of the “S” & “R” mirror-image mixture of citalopram
molecules
• fluoxetine (Prozac, Sarafem, Symbyax- with Zyprexa)
– Very long half-life
– Significant DDIs
– Can be activating
– Conflicting data on use in painful diabetic neuropathy and headache
– 10-80 mg/day (lower doses in hepatic impairment)

41. SSRI antidepressants
• fluvoxamine (Luvox)
– OCD indication
– Multiple significant DDIs
– Conflicting evidence for migraine
– 100-300 mg/day (lower dose or longer dosing interval in hepatic impairment
• paroxetine (Paxil)
– Significant DDIs
– Some reports of associated weight gain
– “Withdrawal” symptoms with missed doses
– 10-75 mg daily (max of 40 mg in renal or hepatic impairment)
• sertraline (Zoloft)
– Moderate DDIs
– Multi-step dosing
– 25-200 mg/day (hepatic impairment consider lower doses)

42. Atypical antidepressants
• venlafaxine (Effexor)
– Similar to TCAs with less safety & side effect concerns
– Can increase blood pressure
– Minimal DDI
– SE with missed doses
– Class B effectiveness in pdn and migraines, unclear in LBP
– Dosing: 75-225 mg/day, reduce dose by 25-50% in renal or hepatic impairment
• duloxetine (Cymbalta)
– SNRI profile minimally dose dependent
– Class B effectiveness for pdn, conditionally recommended for hip and knee OA,
FDA approval for fibromyalgia
– Dosing: 60-120 mg/day (caution in hepatic impairment, do not use if CrCL<30
ml/min

43. Atypical antidepressants
• bupropion (Wellbutrin, Zyban)
– NE, dopamine reuptake inhibition
– Can be activating
– Dosing: 150-450 mg/day (consider reduction in renal and hepatic
impairment)
– Seizure risk in certain patients (↑ risk at ↑ dose)
– Potential DDIs not often significant (except MAOIs)
• Milnacipran (Savella)
– Complex serotonin, NE (α2) activity
– Increased bp and heart rate, headaches, significant GI AE
– FDA approved for the treatment of fibromyalgia
– Dosing: 50-100 mg bid, no adjustments for hepatic impairment,
reduce dose after CrCl <30 ml/min

44. Anticonvulsants
Gabapentin
• FDA approved for postherpetic
neuralgia, conflicting data in
migraines, level B recommendation
in PDN, short term benefit in
radiculopathy
• Anticonvulsant: uncertain
mechanism, gaba mimetic
• Limited intestinal absorption
• Usually well tolerated; serious
adverse effects rare
– dizziness and sedation can occur
• No significant drug interactions
• Usual dosage range for neuropathic
pain up to 3,600 mg/d (tid–qid)*
Pregabalin
• Gaba mimetic
• More reliable oral absorption
• Slightly different side effect profile
• Doses: 75-300mg BID
• Advantages include predictable
absorption across the GI tract.
Not metabolized or protein-
bound. Minimal drug-drug
interactions.
• Multiple studies demonstrate
effective pain relief and decreased
sleep interference in PHN and
PDN
*Not approved by FDA for this use.

46. Antispasmodics
• Consider baclofen or tizanidine or
metaxolone
• Less ideal options include cyclobenzaprine,
carisoprodol and methocarbamol
• Baclofen
– Dosing
• 5 mg orally TID
• Can increase by 15 mg/day every 3
days
• Max 80 mg/day
– ADE: dizziness, N/V, fatigue
• Tizanidine
– Dosing
• 2 mg orally
• Can repeat every 6-8 hours
• Can increase by 2-4 mg/dose every
1-4 days
• Max 36 mg/day
– ADE: xerostomia, dizziness, somnolence
Others
• Acetaminophen
• Topicals
– Lidocaine
– NSAIDS
– Capsaicin
– Menthol
• Over the counter products

47. Medication summary
• Avoid drastic changes in therapy unless for
safety
• Address worsening pain thru psychotropics as
applicable
• Utilize topicals
• Utilize OTC products
• Utilize your local pharmacists to address
financial barriers

48. 48 * This initiative is supported by 48

49. Thank You!
www.weitzmaninstitute.org/coronavirus
49