Central Control of Peripheral Joint Inflammation and Heat Hyperalgesia.
Year: 1994
Type: article
Abstract: Arthritis is a common and disabling problem in our population. Joint inflammation, arthritis, is associated with behavioral changes such as limping, guarding, decreased range of motion, and an increased response to peripheral noxious stimuli (hyperalgesia). For these reasons, experimental animal models have been designed to study various arthritic conditions. The injection of a mixture of kaolin and carrageenan into the knee joint is a model designed to study the acute inflammatory response. These irritants produce a localized joint inflammation and limping and guarding of the limb (Coggeshall et al. 1983; Sluka and Westlund 1992). This arthritis model has been studied in the anesthetized cat (Schaible et al. 1987; Neugebauer and Schaible 1990), anesthetized monkey (Dougherty et al. 1992b; Sluka et al. 1992; Sorkin et al. 1992; Westlund et al. 1992), and awake rat (Sluka and Westlund 1992, 1993a,b,c,d). Neural changes have been observed in both the peripheral and central nervous systems. Sensitization of articular primary afferent fibers (Coggeshall et al. 1983) and dorsal horn neurons (Dougherty et al. 1992b; Neugebauer and Schaible 1990; Schaible et al. 1987) to cutaneous and joint stimuli occurs after induction of arthritis.
From the symptomatic point of view, arthritis can be divided into two components: (1) the inflammation itself (redness, swelling, increased temperature) in and around the joint, and (2) the pain that accompanies this inflammation. Blood-borne or local factors have been considered the sole players in the development of inflammation (Hurley 1983) until relatively recently. There is clear evidence that both the peripheral somatic and sympathetic nervous systems are involved in a variety of inflammatory conditions (see Levine et al. 1988). For example, primary afferent fibers are known to release the inflammatory neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP), into the knee joint (Yaksh et al. 1988; Larsson et al. 1991). These neuropeptides have been found in the exudate in both human arthritic conditions and in animal models of arthritis (Applegren et al. 1991; Larsson et al. 1991; Marshall et al. 1990). In adjuvant arthritis, a chronic inflammatory model, chemical sympathectomies decrease the severity of the arthritis (Levine et al. 1986).
We used the kaolin and carrageenan model of inflammation in our experiments to investigate the involvement of:
spinal excitatory amino acid (EAA) receptors of the non-N-methyl-D-aspartate (non-NMDA) (n = 8) and NMDA (n = 8) types,
spinal gamma-aminobutyric acidA (GABAA) receptors (n = 8),
primary afferent fibers (unilateral dorsal rhizotomy) (n = 6), and
the sympathetic nervous system (surgical and/or chemical sympathectomy) (n = 6)
In rats, the knee joint is injected with a mixture of 0.1 cc of 3% kaolin and 3% carrageenan while animals are briefly anesthetized (Sluka and Westlund 1992). Following induction of arthritis, we assessed pain-related behaviors using paw withdrawal latency (PWL) to radiant heat and a subjective pain rating scale. The degree of inflammation was determined by measuring joint circumference and with thermography. Additionally, we assessed the effects of non-NMDA and NMDA receptors on excitatory amino acid (EAA) release in the dorsal horn. Antagonists were infused into the spinal cord through a microdialysis fiber implanted into the dorsal horn (lamina III–IV of the lumbar [L3–L6] spinal cord). As a control for the localization of the effects of receptor antagonists, a microdialysis fiber was placed into the sacral spinal cord. Untreated arthritic (n = 10) and saline-injected control animals (n = 4) were used for comparison. All experiments were approved by the Animal Care and Use Committee at our institution.
Source: PubMed
Institution: The University of Texas Medical Branch at Galveston
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1469789305