30 The New York Reviewtime scales. Acute conditions, medi-
cal students are taught, last hours to
weeks; subacute ones weeks to months;
chronic ones months to years. These
distinctions are helpful because the
diagnostic possibilities suggested by a
few days of cough as opposed to a few
years of cough, or a week’s fever com-
pared with several months of recurrent
fever, are distinct. Testing everyone in
urgent care for, say, tuberculosis or a
blocked artery just isn’t practical. Tests
are expensive and resource- intensive,
and some can be painful or even harm-
ful. “Tincture of time” sorts out a great
many medical mysteries without over-
taxing the clinician or putting patients
through dubious ordeals.
Our symptoms do not read text-
books, unfortunately: medicine’s lin-
guistic conventions serve as doctors’
shortcuts rather than marking firm bor-
ders. While the terms acute and chronic
pain may be useful in generating a dif-
ferential diagnosis—a list of things
that a patient’s pain could signify—a
growing body of scientific literature
suggests that they are not just long and
short versions of the same fundamental
experience. Saying that chronic pain is
the long- haul version of acute pain may
be like saying that an elephant is a dog
that lives an unusually long time and
doesn’t eat meat.
For one thing, the peripheral nerves
of people experiencing chronic and in-
tractable pain undergo unique develop-
ments not associated with acute pain at
all. One is an electrical change called
long- term hyperexcitability. When hy-
perexcitable nerves experience small
fluctuations in chemical charges across
their cell membranes, this sets off a re-petitive and disproportionate sequence
of electrical “firings,” whereas a typical
cell would only permit one firing and
then enforce an electrical pause. Imag-
ine that you impatiently hit the elevator
button for your desired floor seven or
eight times, thinking it’ll bring you to
your destination faster. A normal ele-
vator “understands” that you just want
to go to the twentieth floor once. An
aberrant, chronic- pain- like elevator
takes you at your word and makes eight
sequential trips to the twentieth floor,
to the consternation of everyone else in
the building.
Even more important, the brain ex-
periencing chronic pain acts quite dif-
ferently than it does during acute pain.
Acute and chronic back pain, for exam-
ple, appear to have such different neu-
romatrices that conceiving of them as
two subtypes under the common head-
ing “back pain” might lead to more
confusion than clarity.
An estimated one in five Americans
has chronic pain, and a third of those
have pain that has “frequently limited
life or work activities” in the previous
three months. A typical therapeu-
tic regimen may include medications
that act on the cascade of cellular re-
sponses causing inflammation, that in-
hibit overexcitable nerve signaling, or
that dampen or amplify pain signals in
neurotransmitters, not to mention po-
tential “hardware” fixes like implanted
neurostimulators, as well as treatments
concerning sleep, exercise, diet, and
mindfulness practices.
Many of those with chronic pain—
including several patients and friends
of mine—feel offended or misunder-
stood when their clinicians suggesttherapeutic approaches that might in-
clude medications such as serotonin-
norepinephrine reuptake inhibitors
(SNRIs) or tricyclic antidepressants
(TCAs), which fall colloquially under
the larger heading of “antidepres-
sants.” Because of this categorization,
people can take such advice as imply-
ing that their pain isn’t real.
In fact there are nerves and neu-
rotransmitters throughout the body—
how else does the brain receive news
of what’s happening beyond its bony
case?—and it is unsurprising that
drugs initially prescribed for psycho-
logical distress should also show some
effect (albeit limited and as yet inade-
quately investigated) on certain kinds
of chronic pain.^2 Duloxetine, for exam-
ple, an SNRI, is approved by the FDA
for treatment of the pain associated
with chronic conditions as seemingly
diverse as osteoarthritis, diabetic neu-
ropathy, and fibromyalgia.
The pain- relieving efficacy of drugs
that may alter the availability of sero-
tonin and norepinephrine—substances
not thought to be central to the way pe-
ripheral nerves sense painful stimuli—
aligns with the neuromatrix model of
chronic pain. The distinct neurosigna-
tures of chronic pain may in fact have
less to do with real- time nociception
(data coming in from peripheral nerve
endings that some tissues are too hot,
too cold, too inflamed, etc.) than with
the deeply patterned ways our brain
processes emotion, memory, and
behavior.In An Anatomy of Pain, Lalkhen wor-
ries that discussing this overlap in the
brain’s responses to pain and to other
forms of distress “may be reinforcing
[patients’] fear that we consider the
pain to be ‘all in their head.’” I, too,
have often been troubled by the indig-
nation expressed by patients in pain
at what they take to be their doctor’s
implication—when antidepressants or
forms of talk therapy are offered, for
example—that they have an illness
pertaining to the psyche. Would having
a troubled mind really be so shameful,
so unassimilable? The extent to which
“believing patients” with chronic pain
has come to mean, in certain patient-
advocacy groups, believing that such
patients do not experience any signifi-
cant mental distress indicates, I think,
the depth of the ongoing social stigma
around disorders of the mind and brain.
For better or worse, the placebo
effect is deeply involved in all these
therapies. This is mainly good news:
it means that the benefit we can derive
from a therapy is greater than the sum
of its constituent molecules. It is an
important part of the success not only
of therapies outside of Western medi-
cine’s traditional ambit (acupuncture,
for example), but also of those squarely
within it. Even opioids have effects that
include both placebo and “nocebo”
(harmful because of patient beliefs and
expectations). One study of the drug
remifentanil, an opioid related to the
better- known fentanyl, found that mak-
ing participants aware of its admin-
istration doubled its analgesic effect
compared with administering it in theabsence of prior cues, whereas falsely
telling participants that the infusion
of the drug had stopped frequently ne-
gated its pain- relieving effects.^3
The downside of placebo effects is
that until we quantify how substantial
they are, we do not know to what extent
we are needlessly enriching pharma-
ceutical companies and exposing peo-
ple to non- negligible pharmacological
risks (including withdrawal) and the
possibility of organ damage (for exam-
ple, from a misuse of acetaminophen).
Measuring how much pain someone
is in, or how much relief they experi-
ence, turns out to be a difficult busi-
ness. As has by now been thoroughly
documented, Purdue Pharma, maker
most famously of OxyContin, worked
assiduously to ensure that safety and
efficacy trials of their opioids would
take place in clinical settings already
influenced to look favorably on them.
Purdue and other pharmaceutical com-
panies pushed for an array of practice
changes that made the assessment and
treatment of pain more central, more
mandatory, and more numerically fo-
cused than it had ever been before.
Many disparate kinds of pain have
tended under this numerical regime to
be lumped into the 0–10 rating system
or a similarly one- dimensional scale.
The problems with this are manifold.
The numbers themselves, of course,
have at best some intrapersonal valid-
ity (my sense of what intensity of pain
merits a 4 might be stable over time)
but no interpersonal validity (two peo-
ple struck in the same place by base-
balls thrown at the same speed might
rate the pain quite differently). Par-
ticularly in a hospital setting, patients
quickly come to understand that when
they are asked to rate their pain, they
are really being asked whether they
want more medication, and perhaps
what kind they would like. This reflects
the way many doctors still write orders
for analgesics in the hospital; e.g., to
give acetaminophen for a pain score of
1–3, five milligrams of oxycodone for
4–6, and ten milligrams of oxycodone
for 7–10.
Most important, the overall flattening
effect of these tools habituates patients
and providers alike to an oversimplifi-
cation of everything we ought to know
or be curious about when it comes to
pain. What Warraich says in The Song
of Our Scars about early- twenty- first-
century medicine’s explosion in opioid
use holds true of the hegemony of the
pain score: it has “erased whatever lit-
tle we knew about the nature of suffer-
ing,” and by stripping out the nuances
of pain studies, it also “exaggerate[s]
the biases that lead to vulnerable peo-
ple’s agony going unattended.”Pain is regarded differently depend-
ing on who’s feeling it. Elaine Scarry
writes in The Body in Pain (1985) that
“to hear that another person has pain
is to have doubt.” The degree of our
doubt is socially constructed. In the
United States and Europe in the nine-
teenth century, with the ruling political(^2) Understanding the full range of uses
of these drugs is still subject to lively
discussion; see, for example, Michelle
Nijhuis, “The Downward Slope,” The
New York Review, March 24, 2022.
(^3) In contrast, some studies of first re-
sponders to drug overdoses suggest that
respiratory changes and alterations in
consciousness they have reported may
at times be amplified by the belief that
they will overdose if exposed to even
trace amounts of fentanyl on the body
of another person.
THE BERLIN PRIZE
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FALL 2022
WILLIAM BAUER
ĀɨɁǹӝɁǹȈɰɽɁɨʰӗĩȶȈʤljɨɰȈɽʰ
ɁǹÇljʤƃǁƃӗ ̧ƃɰřljǼƃɰ
ALEXANDRA CHREITEH
Mellon Bridge Assistant
ĀɨɁǹӝɁǹɨƃƹȈƺƃȶǁ
ȶɽljɨȶƃɽȈɁȶƃȢřȈɰʍƃȢČɽʍǁȈljɰӗ
ěʍǹɽɰĩȶȈʤljɨɰȈɽʰ
SUZANNE L. MARCHAND
9ɁʰǁĀɨɁǹӝɁǹȈɰɽɁɨʰӗ
̧ɁʍȈɰȈƃȶƃČɽƃɽljĩȶȈʤljɨɰȈɽʰ
CLAUDIA RANKINE
ĀɨɁǹӝɁǹ:ɨljƃɽȈʤljŚɨȈɽȈȶǼӗ
ÇljʥťɁɨȟĩȶȈʤljɨɰȈɽʰ
ALEXANDER REHDING
yƃȶȶʰĀljƃƹɁǁʰĀɨɁǹӝɁǹÃʍɰȈƺӗ
ƃɨʤƃɨǁĩȶȈʤljɨɰȈɽʰ
MARY ELISE SAROTTE
¶ɨƃʤȈɰAȈɰɽȈȶǼʍȈɰȃljǁĀɨɁǹӝ
ȈȶɽȃljČƺȃɁɁȢɁǹǁʤƃȶƺljǁ
Studies, Johns Hopkins
ĩȶȈʤljɨɰȈɽʰ
JOSHUA SELLERS
ɰɰɁƺȈƃɽljĀɨɁǹӝɁǹ ̧ƃʥӗ
ɨȈ˃ɁȶƃČɽƃɽljĩȶȈʤljɨɰȈɽʰ
ALMA STEINGART
ɰɰȈɰɽƃȶɽĀɨɁǹӝɁǹȈɰɽɁɨʰӗ
:ɁȢʍȴƹȈƃĩȶȈʤljɨɰȈɽʰ
DAVID TREUER
ĀɨɁǹӝɁǹKȶǼȢȈɰȃӗĩȶȈʤljɨɰȈɽʰ
of Southern California
YING ZHANG
ɰɰɁƺȈƃɽljĀɨɁǹӝɁǹȈɰɽɁɨʰӗ
ěȃljÝȃȈɁČɽƃɽljĩȶȈʤljɨɰȈɽʰ
SPRING 2023
JOHN CONNELLY
Sidney Hellman Ehrman
ĀɨɁǹӝɁǹKʍɨɁɥljƃȶȈɰɽɁɨʰӗ
ĩȶȈʤljɨɰȈɽʰɁǹ:ƃȢȈǹɁɨȶȈƃӗ
Berkeley
HARVEY V. FINEBERG
ĀɨljɰȈǁljȶɽӗ{ɁɨǁɁȶƃȶǁ
9ljɽɽʰÃɁɁɨljyɁʍȶǁƃɽȈɁȶ
TIFFANY N. FLORVIL
ɰɰɁƺȈƃɽljĀɨɁǹӝɁǹȈɰɽɁɨʰӗ
ĩȶȈʤljɨɰȈɽʰɁǹÇljʥÃljʯȈƺɁ
ELA GEZEN
ɰɰɁƺȈƃɽljĀɨɁǹӝɁǹ{ljɨȴƃȶӗ
ĩȶȈʤljɨɰȈɽʰɁǹÃƃɰɰƃƺȃʍɰljɽɽɰӗ
Amherst
LAUREN GROFF
Author
CYMENE HOWE
ĀɨɁǹӝɁǹȶɽȃɨɁɥɁȢɁǼʰӗ
ĄȈƺljĩȶȈʤljɨɰȈɽʰ
LORRIE MOORE
{ljɨɽɨʍǁlj:Ɂȶƃʥƃʰ
řƃȶǁljɨƹȈȢɽĀɨɁǹӝɁǹKȶǼȢȈɰȃ
ƃȶǁ:ɨljƃɽȈʤljŚɨȈɽȈȶǼӗ
řƃȶǁljɨƹȈȢɽĩȶȈʤljɨɰȈɽʰ
ABRAHAM L. NEWMAN
ĀɨɁǹӝɁǹ{Ɂʤljɨȶȴljȶɽӗ
{ljɁɨǼljɽɁʥȶĩȶȈʤljɨɰȈɽʰ
CRISTINA RIVERA GARZA
AȈɰɽȈȶǼʍȈɰȃljǁĀɨɁǹӝɁǹ ̧ƃɽȈȶ
American Studies, and
AȈɨljƺɽɁɨӗ:ɨljƃɽȈʤljŚɨȈɽȈȶǼ
ĀɨɁǼɨƃȴӗĩȶȈʤljɨɰȈɽʰɁǹ
Houston
MARY ELIZABETH WILSON
:ȢȈȶȈƺƃȢĀɨɁǹӝɁǹKɥȈǁljȴȈɁȢɁǼʰ
ƃȶǁ9ȈɁɰɽƃɽȈɰɽȈƺɰӗĩȶȈʤljɨɰȈɽʰ
Ɂǹ:ƃȢȈǹɁɨȶȈƃӗČƃȶyɨƃȶƺȈɰƺɁ
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