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Techniques for assessing knee joint pain in arthritis.

Neugebauer V, Han JS, Adwanikar H, Fu Y, Ji G - Mol Pain (2007)

Bottom Line: The assessment of pain is of critical importance for mechanistic studies as well as for the validation of drug targets.They include measurements of the knee extension angle struggle threshold, hind limb withdrawal reflex threshold of knee compression force, and vocalizations in response to stimulation of the knee.A discussion of pain assessment in humans with arthritis pain conditions concludes this review.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience & Cell Biology, The University of Texas Medical Branch, Galveston, TX 77555-1069, USA. voneugeb@utmb.edu

ABSTRACT
The assessment of pain is of critical importance for mechanistic studies as well as for the validation of drug targets. This review will focus on knee joint pain associated with arthritis. Different animal models have been developed for the study of knee joint arthritis. Behavioral tests in animal models of knee joint arthritis typically measure knee joint pain rather indirectly. In recent years, however, progress has been made in the development of tests that actually evaluate the sensitivity of the knee joint in arthritis models. They include measurements of the knee extension angle struggle threshold, hind limb withdrawal reflex threshold of knee compression force, and vocalizations in response to stimulation of the knee. A discussion of pain assessment in humans with arthritis pain conditions concludes this review.

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Development of punctate (A) and dynamic (B) allodynia and weight bearing deficit (C) following intraarticular injection of monosodium iodoacetate (MIA, 2 mg; ■) MIA or saline (○) in the right knee. (A) Baseline (BL) paw withdrawal thresholds (PWT) were determined in both hind paws prior to injection. PWT to von Frey hair stimulation of the plantar paw surface were assessed on various days post-injection. Results are expressed as median force (g) required for a paw withdrawal in 10 animals per group (vertical bars represent first and third quartiles). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (Mann-Whitney U test) from saline-treated group at each time point. (B) Baseline (BL) paw withdrawal latencies (PWL) to stroking the plantar paw surface with a cotton bud were determined for both hind paws prior to injection. Results are expressed as mean PWL (s) in 10 animals per group (vertical bars represent ± SEM). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (one-way ANOVA followed by Dunnett's posthoc test) from saline-treated group. (C) Baseline (BL) hind paw weight distribution was determined prior to injection. Changes in hind paw weight distribution were assessed on various days post-injection. Results are expressed as mean change in weight distribution (contralateral-ipsilateral) (g) in 10 animals per group (vertical bars represent ± SEM). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (one-way ANOVA followed by Dunnett's posthoc test) from saline-treated group. Reprinted from [46], Copyright 2004, with permission from Elsevier.
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Figure 1: Development of punctate (A) and dynamic (B) allodynia and weight bearing deficit (C) following intraarticular injection of monosodium iodoacetate (MIA, 2 mg; ■) MIA or saline (○) in the right knee. (A) Baseline (BL) paw withdrawal thresholds (PWT) were determined in both hind paws prior to injection. PWT to von Frey hair stimulation of the plantar paw surface were assessed on various days post-injection. Results are expressed as median force (g) required for a paw withdrawal in 10 animals per group (vertical bars represent first and third quartiles). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (Mann-Whitney U test) from saline-treated group at each time point. (B) Baseline (BL) paw withdrawal latencies (PWL) to stroking the plantar paw surface with a cotton bud were determined for both hind paws prior to injection. Results are expressed as mean PWL (s) in 10 animals per group (vertical bars represent ± SEM). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (one-way ANOVA followed by Dunnett's posthoc test) from saline-treated group. (C) Baseline (BL) hind paw weight distribution was determined prior to injection. Changes in hind paw weight distribution were assessed on various days post-injection. Results are expressed as mean change in weight distribution (contralateral-ipsilateral) (g) in 10 animals per group (vertical bars represent ± SEM). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (one-way ANOVA followed by Dunnett's posthoc test) from saline-treated group. Reprinted from [46], Copyright 2004, with permission from Elsevier.

Mentions: Measurements of weight bearing have been used in mono-arthritis models induced in the knee joint by carrageenan, urate, MIA or papain and by surgery (partial meniscectomy). Most commonly, the weight distribution on the two hind paws is measured as the force exerted by each limb on a transducer plate in the floor over a given time period [13,26,43-46]. Weight borne by each hind limb is expressed as percent of body weight [14,44] or percent of weight borne by both hind limbs [13,45]. The ratio [19,43] or difference [46,55] of weight distribution (force) between each hind limb are also calculated. A significant shift of weight from the arthritic site to the contralateral limb, i.e., a weight-bearing deficit, is taken as a pain measure and has been shown in knee joint arthritis models induced by intraarticular MIA [13,14,45,46,55], papain [13], urate [43] and carrageenan [44] and by partial meniscectomy [14,56]. Figure 1 illustrates the weight bearing deficit in rats with MIA-induced knee joint arthritis. These static measurements of weight bearing by the hind limbs typically involve restraining the animals and do not assess the shift of weight distribution to the forelimbs as occurs with hind limb injury such as arthritis [48].


Techniques for assessing knee joint pain in arthritis.

Neugebauer V, Han JS, Adwanikar H, Fu Y, Ji G - Mol Pain (2007)

Development of punctate (A) and dynamic (B) allodynia and weight bearing deficit (C) following intraarticular injection of monosodium iodoacetate (MIA, 2 mg; ■) MIA or saline (○) in the right knee. (A) Baseline (BL) paw withdrawal thresholds (PWT) were determined in both hind paws prior to injection. PWT to von Frey hair stimulation of the plantar paw surface were assessed on various days post-injection. Results are expressed as median force (g) required for a paw withdrawal in 10 animals per group (vertical bars represent first and third quartiles). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (Mann-Whitney U test) from saline-treated group at each time point. (B) Baseline (BL) paw withdrawal latencies (PWL) to stroking the plantar paw surface with a cotton bud were determined for both hind paws prior to injection. Results are expressed as mean PWL (s) in 10 animals per group (vertical bars represent ± SEM). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (one-way ANOVA followed by Dunnett's posthoc test) from saline-treated group. (C) Baseline (BL) hind paw weight distribution was determined prior to injection. Changes in hind paw weight distribution were assessed on various days post-injection. Results are expressed as mean change in weight distribution (contralateral-ipsilateral) (g) in 10 animals per group (vertical bars represent ± SEM). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (one-way ANOVA followed by Dunnett's posthoc test) from saline-treated group. Reprinted from [46], Copyright 2004, with permission from Elsevier.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851005&req=5

Figure 1: Development of punctate (A) and dynamic (B) allodynia and weight bearing deficit (C) following intraarticular injection of monosodium iodoacetate (MIA, 2 mg; ■) MIA or saline (○) in the right knee. (A) Baseline (BL) paw withdrawal thresholds (PWT) were determined in both hind paws prior to injection. PWT to von Frey hair stimulation of the plantar paw surface were assessed on various days post-injection. Results are expressed as median force (g) required for a paw withdrawal in 10 animals per group (vertical bars represent first and third quartiles). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (Mann-Whitney U test) from saline-treated group at each time point. (B) Baseline (BL) paw withdrawal latencies (PWL) to stroking the plantar paw surface with a cotton bud were determined for both hind paws prior to injection. Results are expressed as mean PWL (s) in 10 animals per group (vertical bars represent ± SEM). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (one-way ANOVA followed by Dunnett's posthoc test) from saline-treated group. (C) Baseline (BL) hind paw weight distribution was determined prior to injection. Changes in hind paw weight distribution were assessed on various days post-injection. Results are expressed as mean change in weight distribution (contralateral-ipsilateral) (g) in 10 animals per group (vertical bars represent ± SEM). * P < 0.05, ** P < 0.01, *** P < 0.001 significantly different (one-way ANOVA followed by Dunnett's posthoc test) from saline-treated group. Reprinted from [46], Copyright 2004, with permission from Elsevier.
Mentions: Measurements of weight bearing have been used in mono-arthritis models induced in the knee joint by carrageenan, urate, MIA or papain and by surgery (partial meniscectomy). Most commonly, the weight distribution on the two hind paws is measured as the force exerted by each limb on a transducer plate in the floor over a given time period [13,26,43-46]. Weight borne by each hind limb is expressed as percent of body weight [14,44] or percent of weight borne by both hind limbs [13,45]. The ratio [19,43] or difference [46,55] of weight distribution (force) between each hind limb are also calculated. A significant shift of weight from the arthritic site to the contralateral limb, i.e., a weight-bearing deficit, is taken as a pain measure and has been shown in knee joint arthritis models induced by intraarticular MIA [13,14,45,46,55], papain [13], urate [43] and carrageenan [44] and by partial meniscectomy [14,56]. Figure 1 illustrates the weight bearing deficit in rats with MIA-induced knee joint arthritis. These static measurements of weight bearing by the hind limbs typically involve restraining the animals and do not assess the shift of weight distribution to the forelimbs as occurs with hind limb injury such as arthritis [48].

Bottom Line: The assessment of pain is of critical importance for mechanistic studies as well as for the validation of drug targets.They include measurements of the knee extension angle struggle threshold, hind limb withdrawal reflex threshold of knee compression force, and vocalizations in response to stimulation of the knee.A discussion of pain assessment in humans with arthritis pain conditions concludes this review.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience & Cell Biology, The University of Texas Medical Branch, Galveston, TX 77555-1069, USA. voneugeb@utmb.edu

ABSTRACT
The assessment of pain is of critical importance for mechanistic studies as well as for the validation of drug targets. This review will focus on knee joint pain associated with arthritis. Different animal models have been developed for the study of knee joint arthritis. Behavioral tests in animal models of knee joint arthritis typically measure knee joint pain rather indirectly. In recent years, however, progress has been made in the development of tests that actually evaluate the sensitivity of the knee joint in arthritis models. They include measurements of the knee extension angle struggle threshold, hind limb withdrawal reflex threshold of knee compression force, and vocalizations in response to stimulation of the knee. A discussion of pain assessment in humans with arthritis pain conditions concludes this review.

Show MeSH
Related in: MedlinePlus