Chronic musculoskeletal pain is a major clinical problem and there is a general lack of animal models to study this condition. Carrageenan is commonly used to produce short-lasting acute inflammation and hyperalgesia in animal models. However, the potential of carrageenan to produce chronic, long-lasting hyperalgesia has not been evaluated. In the present study, we investigated the long-term effects of carrageenan injected into joint or muscle in rats. Rats were injected with 0.3, 1 or 3% carrageenan in one knee joint or gastrocnemius muscle and hyperalgesia to mechanical (measured as decreased withdrawal threshold) and heat (measured as decreased withdrawal latency) stimuli of both paws assessed before and at varying times after injection, through 8 weeks. Histological changes were examined only after injection of 3% carrageenan. Three percent carrageenan injected in the muscle or knee produced hyperalgesia to mechanical and heat stimuli ipsilaterally, which lasted 7-8 weeks and spread to the contralateral side 1-2 weeks after injection. One percent carrageenan injected to the knee joint or gastrocnemius muscle, produced hyperalgesia that was shorter-lasting and remained ipsilateral; 0.3% carrageenan injected into the knee joint or gastrocnemius muscle had no effect. Three percent carrageenan injected into the skin surrounding the knee joint did not produce hyperalgesia. A similar pattern of inflammatory changes was observed histologically for both the joint and muscle tissues. Acute inflammation was observed for the first 24 h with edema and neutrophilic infiltration evident as early as 4 h. At 1 week, the inflammation converted to primarily a macrophage response with scattered mast cells. The data suggest that animals injected with 1 or 3% carrageenan in the knee joint or gastrocnemius muscle could be used as models of acute inflammation through 24 h and chronic inflammation after 1 week. Furthermore, 3% carrageenan injected into deep tissues produces hyperalgesia that spreads to the contralateral side, at the same time period as the inflammation transforms from acute to chronic.

/pdf/unilateral-carrageenan-injection-into-muscle-or-joint-3axlrbzhwf.pdf

Unilateral carrageenan injection into muscle or joint induces chronic bilateral hyperalgesia in rats.

Computerized analysis of audible and ultrasonic vocalizations of rats as a standardized measure of pain-related behavior.

A role for substance P in arthritis

Cross-talk between the nervous, endocrine and immune systems exists via regulator molecules, such as neuropeptides, hormones and cytokines. A number of neuropeptides have been implicated in the genesis of inflammation, such as tachykinins and calcitonin gene-related peptide. Development of their receptor antagonists could be a promising approach to anti-inflammatory pharmacotherapy. Anti-inflammatory neuropeptides, such as vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, α-melanocyte-stimulating hormone, urocortin, adrenomedullin, somatostatin, cortistatin, ghrelin, galanin and opioid peptides, are also released and act on their own receptors on the neurons as well as on different inflammatory and immune cells. The aim of the present review is to summarize the most prominent data of preclinical animal studies concerning the main pharmacological effects of ligands acting on the neuropeptide receptors. Promising therapeutic impacts of these compounds as potential candidates for the development of novel types of anti-inflammatory drugs are also discussed.

/pdf/neuropeptide-receptors-as-potential-drug-targets-in-the-103mpxpu72.pdf

Neuropeptide receptors as potential drug targets in the treatment of inflammatory conditions.

http://spinepain.seas.upenn.edu/Lee_2009.pdf

Joint distraction magnitude is associated with different behavioral outcomes and substance P levels for cervical facet joint loading in the rat.

Local neurokinin-1 receptor in the knee joint contributes to the induction, but not maintenance, of arthritic pain in the rat

Background: Recent findings suggest that a coupling between the somatic and sympathetic nervous system is critical not only for the development but also for the maintenance of pain behavioral changes. However, studies on the effect of sympathetic efferent system on sensory receptors in the visceral organ that is more dependent on the autonomic nervous system are lacking. This study examined whether norepinephrine (NE) had an influence on the mechanoreceptors in the feline urinary bladder. Methods: Ten adult male cats were used and anesthetized with α-chloralose and artificially ventilated. A cannula with the pressure transducer was inserted through the urethra to apply mechanical stimuli and monitor the pressure of bladder. A tiny cannula inserted into the bilateral side branches of vesical arteries were used as a route for a NE (10μg bilaterally) injection. Nerve fiber recordings were obtained from the distal stump of the pelvic nerve. Results: After the NE injection, the response of mechanoreceptors (n = 13) to the isotonic pressure stimulus (50-60 mmHg) decreased significantly (p < 0.05) in terms of sensitivity (i.e., ratio of nerve activity change to urinary bladder pressure change). The responses to pressure stimuli after an injection of an α1 adrenoceptor blocker (terazosin) reversed the effect of NE. The responses of mechanoreceptors to isotonic pressure stimulus were not affected significantly by NE with preinjection of an α2 adrenoceptor blocker (yohimbine). Conclusions: These results suggest that NE may have influence on the sensitivity of mechanoreceptors in the normal feline urinary bladder via an α1 adrenoceptor. (Korean J Anesthesiol 2001; 40: 406∼412) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

http://synapse.koreamed.org/Synapse/Data/PDFData/1011KJAE/kjae-40-406.pdf

Jong Moon Hwang

Papers

Local neurokinin-1 receptor in the knee joint contributes to the induction, but not maintenance, of arthritic pain in the rat

Effects of Norepinephrine on the Mechanoreceptors of the Urinary Bladder in the Cat