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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.

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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

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


0 state, which is therefore subject to all sorts of influences.

no pain

10

worst pain imaginable

Situation #1: HEALTHY HUMAN

--psychophysics--

“nociception” – sensitivity to a stimulus

  • Von Frey hairs: demonstration in class

  • threshold

  • magnitude estimation

  • tolerance

VAS

X

Ethics?

Critiques?

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


Situation #2: HEALTHY HUMAN state, which is therefore subject to all sorts of influences.

--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


0 state, which is therefore subject to all sorts of influences.

no pain

10

worst pain imaginable

Situation #3: PATHOLOGY-HUMAN

--psychophysics or pain behavior—

rated by patient

VAS: rate a stimulus or ongoing pain

X

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


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

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


Situation #4: PATHOLOGY-HUMAN 6:00am

--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 6:00am

(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- 6:00am

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. N Engl J Med 1997;336:1197-1201.

CIRCUMCISION

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 6:00am

Assessment of vaginal nociception in the rat

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


Situation #7: PATHOLOGY-ANIMAL-RAT 6:00am

--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 6:00am

--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


ENDOMETRIOSIS 6:00am

shamENDOMETRIOSIS

PROESTRUS

ESTRUS

METESTRUS

DIESTRUS

Situation #7: PATHOLOGY-ANIMAL-RAT

--psychophysics--

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

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 6:00am

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 6:00am

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 6:00am

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


ENDO surgery 6:00amdecreases vocalization thresholds to muscle stimulation to a greater extent in ENDO+stone than stone-only rats.

Vocalization threshold

..but shamENDO surgery decreases vocalization thresholds to muscle stimulation to a lesser extent in shamENDO+stone than in stone-only rats.

THE CONCEPT OF REFERRED PAIN

The same effect occurs for referred muscle nociception.

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


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