measuring pain pain seminar, class # 2, measures, p. 1

Measuring PainMeasuring PainMeasuring PainMeasuring Pain

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

Subjects HUMANS

Conditon HEALTHY PATHOLOGY

Type of measure

-psycho-physics

-pain behaviors

-psycho-physics

-pain behaviors

SubjectsOTHER ANIMALS

(also: non-verbal, cognitively impaired humans)

Conditon HEALTHY PATHOLOGY

Type of measure

-psycho-physics

-pain behaviors

-psycho-physics

-pain behaviors

• 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


X 0

no pain 10worst pain imaginable

VAS

Situation #1: HEALTHY HUMAN --psychophysics--

“nociception” – sensitivity to a stimulus

Von Frey hairs: demonstration in class

threshold magnitude estimation

tolerance

Ethics?

Critiques?


Situation #2: HEALTHY HUMAN--pain behavior—

no obvious stimulus is given

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

From: Prkachin KM. The consistency of facial expressions of pain: a comparison across modalities. Pain 1992;51:297-306.


X 0

no pain 10worst pain imaginable

“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].”

VAS: rate a stimulus or ongoing pain

FACES: rate a stimulus or ongoing pain

Situation #3: PATHOLOGY-HUMAN --psychophysics or pain behavior—

rated by patient


Pain, Lotta 24 Oct 09 6:00am

I have this pain every Monday morning

Situation #4: PATHOLOGY-HUMAN --pain behaviors—

--rated by patient: VAS, MPQ


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


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

--psychophysics--

Many tests, some examplesMany tests, some examples::

Hot plate: withdrawal; vocalization

Von Frey: withdrawal; vocalization

Escape responses

Facial expression (neonates)Ethics?

Critiques?


Situation #5: HEALTHY ANIMAL-

NEONATE (non-verbal human): NEONATE (non-verbal human): psychophysics

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

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. 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.

HEAL LANCE

CIRCUMCISION


Assessment of vaginal nociception in the rat

#5-HEALTHY ANIMAL: RAT-psychophysics#5-HEALTHY ANIMAL: RAT-psychophysics


……an ‘estrogen-dependent’ condition, whosean ‘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.

ENDOMETRIOSIS IN WOMEN

Netter FN. Reproductive System, Ciba, West Caulfield

NJ, 1965.

Situation #7: PATHOLOGY-ANIMAL-RAT Situation #7: PATHOLOGY-ANIMAL-RAT --psychophysics—--psychophysics—

““ANIMAL MODEL (for a clinical condition”ANIMAL MODEL (for a clinical condition”


ENDOMETRIOSIS IN RATSENDOMETRIOSIS IN RATSAutotransplants of pieces of uterine horn in the Autotransplants of pieces of uterine horn in the

abdomen abdomen

(For sham surgery, piece of fat are autotransplanted.)(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 The autotransplants become vascularized and develop into fluid-filled cysts containing develop into fluid-filled cysts containing

inflammatory cells. The cysts grow rapidly over a 1-inflammatory cells. The cysts grow rapidly over a 1-month period, stabilizing by 2 months. They month period, stabilizing by 2 months. They

disappear after ovariectomy and reappear after disappear after ovariectomy and reappear after estrogen replacement.estrogen replacement.

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


0

20

40

60

80

100

0.01 0.1 0.2 0.35 0.45 0.6 0.75 0.85

0

20

40

60

80

100

0.01 0.1 0.25 0.35 0.5 0.65 0.8 0.95

Es

ca

pe

Re

sp

on

se

(%

) Pre

Post

**

**

**

0

20

40

60

80

100

0.01 0.1 0.25 0.35 0.5 0.65 0.8 0.95

Es

ca

pe

Re

sp

on

se

(%

)

0

20

40

60

80

100

0.01 0.1 0.25 0.35 0.5 0.65 0.8 0.95

Es

ca

pe

Re

sp

on

se

(%

)

0

20

40

60

80

100

0.01 0.1 0.25 0.35 0.5 0.65 0.8 0.95

Distention Volume (ml)

Es

ca

pe

Re

sp

on

se

(%

)

0

20

40

60

80

100

0.01 0.1 0.2 0.35 0.45 0.6 0.75 0.85

0

20

40

60

80

100

0.01 0.1 0.2 0.35 0.45 0.6 0.75 0.85

Pre

Post

0

20

40

60

80

100

0.01 0.1 0.2 0.35 0.45 0.6 0.75 0.85

Distention Volume (ml)

ENDOMETRIOSISENDOMETRIOSIS shamENDOMETRIOSISshamENDOMETRIOSIS

METESTRUS

PROESTRUS

DIESTRUS

ESTRUS

The vaginal hyperalgesia is greatest in proestrus (estrogen levels high).

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

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


Situation #6, #8: HEALTH/PATHOLOGYSituation #6, #8: HEALTH/PATHOLOGYANIMALS --pain behaviors--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.]

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.

Pain behaviors evoked by an artifical stone in the

ureter

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.

Class Class demonstration: demonstration: BAT DETECTORBAT DETECTORPain Seminar, Class # 2, MEASURES, p. 14

Situation #6, #8: HEALTH/PATHOLOGYSituation #6, #8: HEALTH/PATHOLOGYANIMALS --pain behaviors--ANIMALS --pain behaviors--

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.

Pain behaviors evoked by an artifical stone in the

ureter


ENDO surgery ENDO surgery increasesincreases pain behaviors pain behaviors

associated with a associated with a ureteral stone….ureteral stone….

..but shamENDO ..but shamENDO surgery surgery decreasesdecreases

them!!them!!““SILENT STONES” SILENT STONES”

THE CONCEPT OF REFERRED PAIN and REFERRED HYPERALGESIA

Diaphragm, Pericardium and Diaphragm, Pericardium and Heart,Heart, Heart, Heart, Digestive tractDigestive tract, , Liver and Gall BladderLiver and Gall Bladder, , Kidney Kidney

and Ureterand Ureter, , Pelvic OrgansPelvic Organs

FROM: http://anatomy.med.umich.edu/surface/abdomen/referred.html


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

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

THE CONCEPT OF REFERRED PAIN

The same effect occurs for referred muscle nociception.

Change in vocalizationthresholds

(left oblique muscle)

0

50

100

150

%

endo+stone stone only sham endo+stone-2 -1 0 1 2 3 4 -2 -1 0 1 2 3 4 -2 -1 0 1 2 3 4 days

||||||||||

||||||||||

||||||||||

--------------------------------------------------

stone stone stone

Voc

aliz

atio

n th

resh

old

ENDO surgery ENDO surgery decreases vocalization decreases vocalization thresholdsthresholds to muscle stimulation to a to muscle stimulation to a greater greater extentextent in ENDO+stone than stone-only rats. in ENDO+stone than stone-only rats.

..but shamENDO surgery ..but shamENDO surgery decreases vocalization decreases vocalization thresholds to muscle stimulation to athresholds to muscle stimulation to a lesser lesser

extent extent in shamENDO+stone than in stone-only in shamENDO+stone than in stone-only rats.rats.


measuring pain pain seminar, class # 2, measures, p. 1

Documents

measuring pain pain

pain point

pain expression

mechanisms of pain

pain behaviors psycho

patient pain seminar

ongoing pain situation

mpq pain seminar