Measuring Pain

Pain Seminar, Class # 2, MEASURES, p. 1

 What we measure is a behavioral index of a presumed
pain state, which is therefore subject to all sorts of
influences.
Nevertheless, if we want to understand mechanisms of
pain (i.e., what produces it) or how to treat it, we have to
be able to measure it quantifiably in health and disease,
and we have to be able to model it in other animals (to help
other animals as well as humans).
There are two basic assessment strategies:
Psychophysics: relates stimulus to behavior (i.e., a
stimulus has to be delivered and a response has to be
measured).
Pain Behaviors: the perception is ongoing; stimuli not
given.
SO, WE HAVE

Subjects HUMANS
Conditon HEALTHY PATHOLOGY
Type of -psycho- -pain -psycho- -pain
measure physics behaviors physics behaviors

Subjects OTHER ANIMALS

(also: non-verbal, cognitively impaired humans)
Conditon HEALTHY PATHOLOGY
Type of -psycho- -pain -psycho- -pain
measure physics behaviors physics behaviors

Pain Seminar, Class # 2, MEASURES, p. 2

 Situation #1: HEALTHY HUMAN
--psychophysics--
nociception sensitivity to a stimulus

Von Frey hairs: demonstration in class

threshold

magnitude estimation

tolerance

VAS

0
X 10
no pain worst pain
imaginable

Ethics?
Critiques?

Pain Seminar, Class # 2, MEASURES, p. 3

 Situation #2: HEALTHY HUMAN
--pain behavior
no obvious stimulus is given

From: Prkachin KM. The consistency of facial expressions of

pain: a comparison across modalities. Pain 1992;51:297-306.

? OUCH!!!
? Heart rate; blood pressure
? Pupil dilation, sweating
? Moaning
? Grimaces
? Postures

Pain Seminar, Class # 2, MEASURES, p. 4

 Situation #3: PATHOLOGY-HUMAN
--psychophysics or pain behavior
rated by patient

VAS: rate a stimulus or ongoing pain

0
X 10
no pain worst pain
imaginable

FACES: rate a stimulus

or ongoing pain

These faces show how much something can hurt.

This face [point to left-most face] shows no pain. The faces
show more and more pain [point to each from left to right] up
to this one [point to right-most face] - it shows very much
pain.
Point to the face that shows how much you hurt [right now].

Pain Seminar, Class # 2, MEASURES, p. 5

 Situation #4: PATHOLOGY-HUMAN
--pain behaviors
--rated by patient: VAS, MPQ
Pain, Lotta 24 Oct 09 6:00am

I have this pain

every Monday
morning

Pain Seminar, Class # 2, MEASURES, p. 6

 Situation #4: PATHOLOGY-HUMAN
--other types of pain behaviors
--rated by patient-

VAS (by observer);

grimaces;
# moans;
heart rate;
blood pressure;
respiratory rate; etc.

BUT: consider

Pain Seminar, Class # 2, MEASURES, p. 7

 Situation #5: HEALTHY ANIMAL
(also: non-verbal, cognitively-impaired humans)
--psychophysics--

Many tests, some examples:

Hot plate: withdrawal; vocalization
Von Frey: withdrawal; vocalization
Escape responses
Facial expression (neonates)

Ethics?
Critiques?

Pain Seminar, Class # 2, MEASURES, p. 8

 Situation #5: HEALTHY ANIMAL-
NEONATE (non-verbal human): psychophysics

Grunau RV, Craig KD. Pain expression in neonates: facial action and cry. Pain. 1987;28:395-410.

HEAL LANCE

Taddio A, Stevens B, Craig K, Rastogi P, Ben-David S, Shennan A, Mulligan P,

Koren G. Efficacy and safety of lidocaine-prilocaine cream for pain during CIRCUMCISION
circumcision. N Engl J Med 1997;336:1197-1201.
Neonatal circumcision is a painful surgical procedure often performed without analgesia. We assessed the efficacy
and safety of 5 percent lidocaine-prilocaine cream (Emla) in neonates undergoing circumcision. METHODS: We carried
out a double-blind, randomized, controlled trial in 68 full-term male neonates: 38 were assigned to receive lidocaine-
prilocaine cream, and 30 to receive placebo. One gram of lidocaine-prilocaine or placebo cream was applied to the
penis under an occlusive dressing for 60 to 80 minutes before circumcision. Behavioral (facial activity and time spent
crying) and physiologic (heart rate and blood pressure) responses were recorded during the procedure. Blood samples
were obtained at various times after drug application for measurements of methemoglobin and plasma lidocaine,
prilocaine, and o-toluidine (a metabolite of prilocaine). RESULTS: A total of 68 and 59 neonates were included in the
safety and efficacy analyses, respectively. Demographic characteristics such as gestational age and birth weight did not
differ between the lidocaine-prilocaine and placebo groups. During circumcision, the neonates in the lidocaine-
prilocaine group had less facial activity (P= 0.01), spent less time crying (P<0.001), and had smaller increases in heart
rate (P=0.007) than the neonates in the placebo group. Facial-activity scores were 12 to 49 percent lower during
various steps of the procedure in the lidocaine-prilocaine group. As compared with neonates in the placebo group,
infants in the lidocaine-prilocaine group cried less than half as much and had heart-rate increases of 10 beats per
minute less. Blood methemoglobin concentrations (expressed as a percentage of the hemoglobin concentration) were
similar (1.3 percent) in both groups. Lidocaine and prilocaine were detected in plasma in 23 (61 percent) and 21 (55
percent) of the infants treated with lidocaine-prilocaine cream, respectively. CONCLUSIONS: Lidocaine-prilocaine
cream is efficacious and safe for the prevention of pain from circumcision in neonates.

Pain Seminar, Class # 2, MEASURES, p. 9

 #5-HEALTHY ANIMAL: RAT-psychophysics

Assessment of vaginal nociception in the rat

Pain Seminar, Class # 2, MEASURES, p. 10

 Situation #7: PATHOLOGY-ANIMAL-RAT
--psychophysics
ANIMAL MODEL (for a clinical condition

ENDOMETRIOSIS IN WOMEN

Netter FN.
Reproductive
System, Ciba,
West Caulfield
NJ, 1965.

an estrogen-dependent condition, whose

Signs: growths of endometrial tissue in abnormal
locations
Symptoms: reduced fertility, severe dysmenorrhea,
dyspareunia, dyschezia, chronic pelvic pain
Other: can co-occur with interstitial cystitis, irritable
bowel syndrome, ureteral and kidney stones,
temporomandibular disorder, migraine, fibromyalgia,
vulvodynia.

Pain Seminar, Class # 2, MEASURES, p. 11

 Situation #7: PATHOLOGY-ANIMAL MODEL
--psychophysics--

ENDOMETRIOSIS IN RATS
Autotransplants of pieces of uterine horn in the abdomen
(For sham surgery, piece of fat are autotransplanted.)

This model was originally developed by Vernon and Wilson:

Vernon MW, Wilson EA. Studies on the surgical induction of
endometriosis in the rat. Fertil Steril 44;1985:684-694.

The autotransplants become vascularized and develop

into fluid-filled cysts containing inflammatory cells. The
cysts grow rapidly over a 1-month period, stabilizing by
2 months. They disappear after ovariectomy and
reappear after estrogen replacement.
Pain Seminar, Class # 2, MEASURES, p. 12
 Situation #7: PATHOLOGY-ANIMAL-RAT
--psychophysics--
The vaginal hyperalgesia is greatest in proestrus (estrogen levels high).

ENDOMETRIOSIS shamENDOMETRIOSIS
100 100
Escape Response (%) Pre Pre
Post 80 Post
80

60 60
PROESTRUS 40 *
**
40

20
* 20
**
0 0
0.01 0.1 0.25 0.35 0.5 0.65 0.8 0.95 0.01 0.1 0.2 0.35 0.45 0.6 0.75 0.85

100 100
Escape Response (%)

80 80

60 60

ESTRUS 40 40

20 20

0 0
0.01 0.1 0.25 0.35 0.5 0.65 0.8 0.95 0.01 0.1 0.2 0.35 0.45 0.6 0.75 0.85

100 100
Escape Response (%)

80 80

60 60

METESTRUS 40 40

20 20

0 0
0.01 0.1 0.25 0.35 0.5 0.65 0.8 0.95 0.01 0.1 0.2 0.35 0.45 0.6 0.75 0.85

100 100
Escape Response (%)

80 80

DIESTRUS 60 60

40 40

20 20

0 0
0.01 0.1 0.25 0.35 0.5 0.65 0.8 0.95 0.01 0.1 0.2 0.35 0.45 0.6 0.75 0.85
Distention Volume (ml) Distention Volume (ml)

FROM: Cason A, Samuelson C, Berkley KJ. Horm Behav 2003;44:123-131

Pain Seminar, Class # 2, MEASURES, p. 13
 Situation #6, #8: HEALTH/PATHOLOGY
ANIMALS --pain behaviors--

Hard to study.
How do you know if your dog or a newborn is in pain?
Most work so far has been done in animals the context of a
known pathophysiological condition.
Little has been done in neonates or other non-verbal humans.
[Example: Terstegen C, Koot HM, de Boer JB, Tibboel D. Measuring pain in children with cognitive impairment: pain
response to surgical procedures. Pain. 2003 May;103(1-2):187-98.]

Pain behaviors evoked by

cutting the sciatic nerve.
Attal N, Jazat F, Kayser V, Guilbaud
G. Further evidence for 'pain-related'
behaviours in a model of unilateral
peripheral mononeuropathy. Pain
1990;41:235-51.

Pain behaviors evoked by an

artifical stone in the ureter

Giamberardino MA, Valente R, De Bigontina

P, Vecchiet L. Artifical ureteral calculosis in
rats: behavioral characterization of visceral
pain episodes and their relationship with
referred lumbar muscle hyperalgesia. Pain
(1995) 61:459-469.

Class demonstration:
BAT DETECTOR
Pain Seminar, Class # 2, MEASURES, p. 14
 Situation #6, #8: HEALTH/PATHOLOGY
ANIMALS --pain behaviors--

Pain behaviors evoked by an

artifical stone in the ureter

Giamberardino MA, Valente R, De Bigontina

P, Vecchiet L. Artifical ureteral calculosis in
rats: behavioral characterization of visceral
pain episodes and their relationship with
referred lumbar muscle hyperalgesia. Pain
(1995) 61:459-469.

ENDO surgery increases

pain behaviors associated
with a ureteral stone.

..but shamENDO
surgery decreases
them!!
SILENT STONES

Pain Seminar, Class # 2, MEASURES, p. 15

 THE CONCEPT OF REFERRED PAIN
and REFERRED HYPERALGESIA

Diaphragm, Pericardium and Heart,

Heart, Digestive tract, Liver and
Gall Bladder, Kidney and Ureter,
Pelvic Organs
FROM: http://anatomy.med.umich.edu/surface/abdomen/referred.html

Pain Seminar, Class # 2, MEASURES, p. 16

 THE CONCEPT OF REFERRED PAIN
The same effect occurs for referred muscle nociception.

ENDO surgery decreases vocalization thresholds

to muscle stimulation to a greater extent in
ENDO+stone
Changethan
in stone-only rats.
vocalization
thresholds
(left oblique muscle)
Vocalization threshold

stone stone stone

150
% | | |
| | |
| | |
100 --------------------------------------------------
| | |
| | |
| | |
50 | | |
| | |
| | |
0 | | |
..but shamENDO
-2 -1 0 1 2 3 4surgery
-2 -1 0 1decreases
234 -2 -1 0 1vocalization
2 3 4 days
thresholdsendo+stone
to muscle stimulation
stone only shamto a endo+stone
lesser extent
in shamENDO+stone than in stone-only rats.

Giamberardino MA, Berkley KJ, Affaitati G, Lerza R, Centurione L,

Lapenna D, Vecchiet L. Pain. 2002;95:247-257.

Pain Seminar, Class # 2, MEASURES, p. 17