Allodynia and Hyperalgesia in Adjuvant-Induced Arthritic Rats: Time Course of Progression and Efficacy of Analgesics

Abstract

The complete Freund's adjuvant (CFA)-induced arthritic rat model has extensively served as a laboratory model in the study of arthritic pain. However, the time courses of allodynia and hyperalgesia and the efficacies of different analgesics have not fully been analyzed in this model. Mechanical allodynia, thermal and joint hyperalgesia, and other disease development parameters (body weight, mobility, paw volume, and joint stiffness) were measured on postinoculation days (PIDs) 0 to 28 in rats. Acute analgesic efficacies of drugs were evaluated on PID 9 when degrees of allodynia, hyperalgesia, and joint stiffness in the ipsilateral paw reached almost the maximum, although those in the contralateral paw changed only slightly. In the ipsilateral paw, thermal hyperalgesia reached the maximum on PID 1, whereas mechanical allodynia and joint hyperalgesia progressively developed during the first 7 or 8 days, being tuned in to arthritis development. In the contralateral paw, thermal hyperalgesia never occurred, whereas mechanical allodynia and joint hyperalgesia developed after PID 11. Morphine and tramadol had full efficacies for all the pain parameters tested at sedation-inducing doses. Indomethacin and diclofenac significantly but partially improved thermal and joint hyperalgesia. Amitriptyline significantly reduced thermal and joint hyperalgesia only at sedation-inducing dose. Acetaminophen, carbamazepine, and gabapentin had, at the most, very small efficacies. In conclusion, the present study provided integrated information about the time course of pain and other disease development parameters in the CFA-induced arthritic rats, and clarified acute efficacies of different categories of analgesics for the allodynia and hyperalgesia.The complete Freund's adjuvant (CFA)-induced arthritic rat model has extensively served as a laboratory model in the study of arthritic pain. Mechanical allodynia, thermal hyperalgesia and pain on joint movement (joint hyperalgesia), which are prominent features in arthritic pain, have proved to be present in it (Tatsuo et al., 1994;Jasmin et al., 1998;Bertorelli et al., 1999). The time courses of their progression after the CFA inoculation, however, have not been fully analyzed. The first aim in the present study, therefore, was to provide integrated information about the time courses of pain (mechanical allodynia, thermal hyperalgesia, and joint hyperalgesia) and other disease development (body weight, mobility, paw volume, and joint stiffness) parameters after the CFA inoculation into the single hind paw in rats. Surprisingly, there are no studies that have fully evaluated the analgesic efficacies of different categories of analgesics on mechanical allodynia, thermal hyperalgesia, and joint hyperalgesia in the CFA-induced arthritic rat model. The second aim in the present study, therefore, was to investigate this issue. Antipyretics (e.g., acetaminophen) and nonsteroidal anti-inflammatory drugs (e.g., indomethacin and diclofenac) are the first line drugs in the treatment of arth...

Psidium guajava leaves decrease arthritic symptoms in adjuvant-induced arthritic rats

“…Freund's complete adjuvant-induced arthritis is a well established rat model and has been widely used for many years for evaluation of the anti-inflammatory and anti-arthritic potential of various agents. (10,11) Guava leaves has the potential to be developed as an antiarthritic drug. The present study aimed to evaluate the anti-arthritic activity of the ethanol extract of the leaves of Psidium guajava (EEPG) against complete Freund's adjuvant (CFA) induced arthritis in rats, especially with reference to its anti-inflammatory properties, using dexamethasone as reference drug.…”

Role of peripheral μ‐opioid receptors in arthritis: Are they potential targets for therapy?

“…This approach evokes acute subcutaneous inflammation at the site of injection within a few hours, while arthritis develops ipsilaterally, mainly in the tibiotarsal joint, by the seventh or eighth day after injection. On the contralateral side, much slighter arthritis symptoms develop, from the ninth day through the eleventh day (10)(11)(12). In contrast, CFA can be injected intradermally into the base of the tail to evoke polyarthritis with equal intensity on both sides but mainly in the tibiotarsal joints within 1 week, without soft tissue inflammation of the paws.…”

“…Because systemic (intravenous or intraperitoneal) or central nervous system administration of opioids can result in severe side effects such as disruption of cognitive and motor functions, confusion, hallucinations, or vomiting (10,14), peripheral administration of opioids during periods of inflammation has been proposed (3,4,6). Inflammation increases the number of sensory nerve terminals and disrupts the perineurium, the diffusion barrier for hydrophilic substances such as endogenous or exogenous opioids (15).…”

“…Many reports indicate that, under conditions of inflammation, both the expression of -opioid receptors in the dorsal root ganglia and their anterograde axonal transport toward the peripheral terminals of these primary sensory neurons are enhanced (3,4,6,10,11,20,21). Increased axonal transport is preceded by up-regulation of messenger RNA (mRNA) transcription in response to inflammation, which is dependent on neuronal electrical activity (21).…”

“…These receptors could mediate the antiinflammatory effect of intraarticularly injected morphine in chronic joint inflammation (4,6). Based on these data, several studies have focused on the peripheral opioidergic system as a novel target for the treatment of inflammatory pain such as that occurring in patients with rheumatoid arthritis (3,4,6,10,11).…”