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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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Increased audible and ultrasonic vocalizations in the K/C model of arthritic pain. (A, B) Original recordings of ultrasonic vocalizations evoked by innocuous (upper trace) and noxious (lower trace) stimulation of the knee joint in a rat before (A) and after (B) induction of arthritis with intraarticular kaolin and carrageenan injections. Mechanical stimuli were applied for 15 s; duration of the recording period was 1 min. Vocalizations during and after stimulation (VDS and VAD, respectively) were analyzed separately. (C) Duration of audible and ultrasonic VDS increased significantly 6 h after induction of arthritis compared to the values measured in the same animals before arthritis (n = 16). Stimuli of innocuous (left side) and noxious (right side) intensities evoked VDS of longer duration in arthritic animals compared to controls. (D) Duration of ultrasonic, but not audible, VAD following innocuous (left) and noxious (right) stimuli increased significantly in the arthritis pain model (6 h postinduction; n = 16). Symbols and error bars represent mean ± SE. ** P < 0.01, *** P < 0.001. Reprinted from Han JS & Neugebauer V [54]. PAIN 2005;113-211-222. Used with permission from the International Association for the Study of Pain®.
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Figure 3: Increased audible and ultrasonic vocalizations in the K/C model of arthritic pain. (A, B) Original recordings of ultrasonic vocalizations evoked by innocuous (upper trace) and noxious (lower trace) stimulation of the knee joint in a rat before (A) and after (B) induction of arthritis with intraarticular kaolin and carrageenan injections. Mechanical stimuli were applied for 15 s; duration of the recording period was 1 min. Vocalizations during and after stimulation (VDS and VAD, respectively) were analyzed separately. (C) Duration of audible and ultrasonic VDS increased significantly 6 h after induction of arthritis compared to the values measured in the same animals before arthritis (n = 16). Stimuli of innocuous (left side) and noxious (right side) intensities evoked VDS of longer duration in arthritic animals compared to controls. (D) Duration of ultrasonic, but not audible, VAD following innocuous (left) and noxious (right) stimuli increased significantly in the arthritis pain model (6 h postinduction; n = 16). Symbols and error bars represent mean ± SE. ** P < 0.01, *** P < 0.001. Reprinted from Han JS & Neugebauer V [54]. PAIN 2005;113-211-222. Used with permission from the International Association for the Study of Pain®.

Mentions: Rodents vocalize in the audible and ultrasonic ranges. When evoked by noxious stimuli, audible vocalizations represent a nocifensive reaction whereas ultrasonic vocalizations in the 22 kHz range reflect an emotional-affective response [51,54]. The threshold of audible vocalizations has been measured by compressing the knee of manually restrained rats with a calibrated forceps as described above [33]. Vocalization thresholds are significantly decreased for one week in rats with a K/C arthritis (see Figure 2) and for two weeks in the CFA knee joint arthritis model [33]. A recording chamber and computerized analysis system has been developed to measure simultaneously audible and ultrasonic vocalizations evoked by stimulation of the knee [51,54]. Rate and duration of audible and ultrasonic vocalizations are increased in rats with a K/C knee joint arthritis [51]. It should be noted that the functional relationship between audible and ultrasonic vocalizations, which are generated by different neural mechanisms, has not been addressed in these studies. Vocalizations that occur during stimulation (VDS) and vocalizations that outlast the stimulus (vocalization afterdischarges, VAD) have also been analyzed separately. VDS are organized in the brainstem at the medullary level whereas VAD are organized in the limbic forebrain, including the amygdala. Figure 3 shows that both VDS and VAD increase in rats with a K/C arthritis [54].


Techniques for assessing knee joint pain in arthritis.

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

Increased audible and ultrasonic vocalizations in the K/C model of arthritic pain. (A, B) Original recordings of ultrasonic vocalizations evoked by innocuous (upper trace) and noxious (lower trace) stimulation of the knee joint in a rat before (A) and after (B) induction of arthritis with intraarticular kaolin and carrageenan injections. Mechanical stimuli were applied for 15 s; duration of the recording period was 1 min. Vocalizations during and after stimulation (VDS and VAD, respectively) were analyzed separately. (C) Duration of audible and ultrasonic VDS increased significantly 6 h after induction of arthritis compared to the values measured in the same animals before arthritis (n = 16). Stimuli of innocuous (left side) and noxious (right side) intensities evoked VDS of longer duration in arthritic animals compared to controls. (D) Duration of ultrasonic, but not audible, VAD following innocuous (left) and noxious (right) stimuli increased significantly in the arthritis pain model (6 h postinduction; n = 16). Symbols and error bars represent mean ± SE. ** P < 0.01, *** P < 0.001. Reprinted from Han JS & Neugebauer V [54]. PAIN 2005;113-211-222. Used with permission from the International Association for the Study of Pain®.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Increased audible and ultrasonic vocalizations in the K/C model of arthritic pain. (A, B) Original recordings of ultrasonic vocalizations evoked by innocuous (upper trace) and noxious (lower trace) stimulation of the knee joint in a rat before (A) and after (B) induction of arthritis with intraarticular kaolin and carrageenan injections. Mechanical stimuli were applied for 15 s; duration of the recording period was 1 min. Vocalizations during and after stimulation (VDS and VAD, respectively) were analyzed separately. (C) Duration of audible and ultrasonic VDS increased significantly 6 h after induction of arthritis compared to the values measured in the same animals before arthritis (n = 16). Stimuli of innocuous (left side) and noxious (right side) intensities evoked VDS of longer duration in arthritic animals compared to controls. (D) Duration of ultrasonic, but not audible, VAD following innocuous (left) and noxious (right) stimuli increased significantly in the arthritis pain model (6 h postinduction; n = 16). Symbols and error bars represent mean ± SE. ** P < 0.01, *** P < 0.001. Reprinted from Han JS & Neugebauer V [54]. PAIN 2005;113-211-222. Used with permission from the International Association for the Study of Pain®.
Mentions: Rodents vocalize in the audible and ultrasonic ranges. When evoked by noxious stimuli, audible vocalizations represent a nocifensive reaction whereas ultrasonic vocalizations in the 22 kHz range reflect an emotional-affective response [51,54]. The threshold of audible vocalizations has been measured by compressing the knee of manually restrained rats with a calibrated forceps as described above [33]. Vocalization thresholds are significantly decreased for one week in rats with a K/C arthritis (see Figure 2) and for two weeks in the CFA knee joint arthritis model [33]. A recording chamber and computerized analysis system has been developed to measure simultaneously audible and ultrasonic vocalizations evoked by stimulation of the knee [51,54]. Rate and duration of audible and ultrasonic vocalizations are increased in rats with a K/C knee joint arthritis [51]. It should be noted that the functional relationship between audible and ultrasonic vocalizations, which are generated by different neural mechanisms, has not been addressed in these studies. Vocalizations that occur during stimulation (VDS) and vocalizations that outlast the stimulus (vocalization afterdischarges, VAD) have also been analyzed separately. VDS are organized in the brainstem at the medullary level whereas VAD are organized in the limbic forebrain, including the amygdala. Figure 3 shows that both VDS and VAD increase in rats with a K/C arthritis [54].

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