Pain mechanisms in animal models of rheumatoid arthritis
-
Christina Christianson
Rheumatoid arthritis (RA) is chronic disease affecting 1% of the population. It is characterized by infiltration of inflammatory cells into the joints, synovial neovascularization and proliferation of fibroblasts and bone erosion. Clinically the disease is evident as joint inflammation, swelling and progressive joint destruction. Of importance, pain is one of the most bothersome symptoms reported by RA patients. Autoantibodies to type II collagen (CII) and glucose-6- phosphate isomerase (GPI) are detected in serum of 70% and 20% of the RA patients, respectively. Intraperitoneal injection of these antibodies to mice rapidly induces arthritis-like symptoms and generates a joint pathology that resembles human RA. While collagen antibody-induced arthritis (CAIA) and K/BxN serum transfer (GPI antibody-mediated) are common models in the rheumatology field, they have not been evaluated as models of arthritis-induced pain. Data from our studies in which pain behavior (tactile and cold allodynia) and the analgesic effect of ketorolac (cyclooxygenase inhibitor), etanercept (TNF inhibitor) and gabapentin were examined will be presented. In brief, we observed that both injection of CII and GPI antibodies caused induction of clinical signs of arthritis including joint swelling and redness of the paws, and that this inflammatory state gave rise to a robust, and reproducible allodynia. Interestingly, the allodynia outlasted the signs of joint inflammation. Of note, while intraperitoneal injection of ketorolac, etanercept and gapapentin attenuated arthritis-induced allodynia during the inflammatory phase, only gabapentin had antiallodynic effect in the “post-inflammatory” phase. Spinal activation of astrocytes and microglia was assessed as these cells have been implicated to play a role in the maintenance of hypersensitivity in experimental models of persistent pain. Experiments in which microglia and astrocyte activity was assessed using quantitative real time PCR and immunohistochemistry indicated activation of spinal glia in both models.
In summary, our work demonstrates that the CAIA and K/BxN arthritis models generate robust and highly reproducible allodynia. Based on the resemblance with human pathology these models may become important assets in dissecting the mechanisms that drive arthritis-induced pain, both during peak and remittent phases of the disease.
Supported by: Swedish Research Council, Reumatikerförbundet, Swedish foundation for strategic research, Olle Engkvist byggmästare foundation, International Association for Studies of Pain, EU - Marie Curie and NIH.
© 2010 Scandinavian Association for the Study of Pain
Articles in the same Issue
- Editorial comment
- Functional brain imaging of acute postoperative pain
- Clinical pain research
- Brain activation due to postoperative pain from the right hand measured with regional cerebral blood flow using positron emission tomography
- Editorial comment
- Long-term low-dose transdermal buprenorphine therapy for chronic noncancer pain
- Original experimental
- A 6-months, randomised, placebo-controlled evaluation of efficacy and tolerability of a low-dose 7-day buprenorphine transdermal patch in osteoarthritis patients naïve to potent opioids
- Editorial comment
- Repeated nociceptive stimulation for detecting drug effects
- Original experimental
- The effects of gabapentin in human experimental pain models
- Editorial comment
- Whether the weather influences pain: High prevalence of chronic pain in Iceland and Norway: Common genes? Or lack of sunshine and vitamin D?
- Observational studies
- A population based study of the prevalence of pain in Iceland
- Editorial comment
- Swedish nurses are prone to chronic shoulder and back pain because of miserable working conditions and poor leadership?
- Observational studies
- Predicting of pain, disability, and sick leave regarding a non-clinical sample among Swedish nurses
- Abstracts
- Trigeminal neuralgia or odontogenic pain
- Abstracts
- What’s wrong with animal models of pain?
- Abstracts
- Immunotherapy for neuroblastoma elicits a complement dependent whole body allodynia
- Abstracts
- Pain mechanisms in animal models of rheumatoid arthritis
- Abstracts
- Translating basic research to pharmacological treatment of neuropathic pain
- Abstracts
- Free Poster Presentations: Forearm heat pain does not inhibit electrically induced tibialis anterior muscle pain
- Abstracts
- Offset analgesia evoked by non-contact thermal stimulator
- Abstracts
- Inhibition of FAAH reverses spinal LTP
- Abstracts
- Hyperexcitable C-nociceptors in human paroxysmal pain
- Abstracts
- Pain sensitivity and experimentally induced sensitization in red haired women
- Abstracts
- How are opioids used in Norway? Persistent use, utilization of depot formulation and age profile in non-palliation patients
- Abstracts
- To which extent does incident and persistent use of weak opioids predict problematic opioid use?
- Abstracts
- Is transdermal buprenorphine for chronic non-malignant pain used long term without co-medication with other potentially addictive drugs?
- Abstracts
- Prostaglandin E2 production in synovial tissue and acute postoperative pain after knee arthroscopy
- Abstracts
- Girl presenting with oesophageal spasm pain after fundoplication
- Abstracts
- Epidemiology of persistent postoperative pain: Association of persistent pain and sensory abnormalities
- Abstracts
- Cost–benefit of a 13-week multidiciplinary rehabilitation course for chronic non-malignant pain patients
- Abstracts
- A novel and effective treatment modality for medically unexplained pain
- Abstracts
- Somatocognitive therapy in the management of chronic gynaecological pain. A review of current approach and historical background
- Abstract
- The Manual Intervention Trial (MINT)—The effect of various combinations of naprapathic manual therapy. The study protocol of a randomized controlled trial
- Abstracts
- The experience of chronic pain, loss and grief
- Abstracts
- Effect of buprenorphine and fentanyl in experimental induced superficial, deep and hyperalgesic pain
- Abstract
- Pretreatment with opioids enhances afferent induced long-term potentiation in the rat dorsal horn
- Abstracts
- Pigs in pain—Porcine behavioural responses towards mechanical nociceptive stimulation directed at the hind legs
- Abstracts
- A human experimental bone pain model
Articles in the same Issue
- Editorial comment
- Functional brain imaging of acute postoperative pain
- Clinical pain research
- Brain activation due to postoperative pain from the right hand measured with regional cerebral blood flow using positron emission tomography
- Editorial comment
- Long-term low-dose transdermal buprenorphine therapy for chronic noncancer pain
- Original experimental
- A 6-months, randomised, placebo-controlled evaluation of efficacy and tolerability of a low-dose 7-day buprenorphine transdermal patch in osteoarthritis patients naïve to potent opioids
- Editorial comment
- Repeated nociceptive stimulation for detecting drug effects
- Original experimental
- The effects of gabapentin in human experimental pain models
- Editorial comment
- Whether the weather influences pain: High prevalence of chronic pain in Iceland and Norway: Common genes? Or lack of sunshine and vitamin D?
- Observational studies
- A population based study of the prevalence of pain in Iceland
- Editorial comment
- Swedish nurses are prone to chronic shoulder and back pain because of miserable working conditions and poor leadership?
- Observational studies
- Predicting of pain, disability, and sick leave regarding a non-clinical sample among Swedish nurses
- Abstracts
- Trigeminal neuralgia or odontogenic pain
- Abstracts
- What’s wrong with animal models of pain?
- Abstracts
- Immunotherapy for neuroblastoma elicits a complement dependent whole body allodynia
- Abstracts
- Pain mechanisms in animal models of rheumatoid arthritis
- Abstracts
- Translating basic research to pharmacological treatment of neuropathic pain
- Abstracts
- Free Poster Presentations: Forearm heat pain does not inhibit electrically induced tibialis anterior muscle pain
- Abstracts
- Offset analgesia evoked by non-contact thermal stimulator
- Abstracts
- Inhibition of FAAH reverses spinal LTP
- Abstracts
- Hyperexcitable C-nociceptors in human paroxysmal pain
- Abstracts
- Pain sensitivity and experimentally induced sensitization in red haired women
- Abstracts
- How are opioids used in Norway? Persistent use, utilization of depot formulation and age profile in non-palliation patients
- Abstracts
- To which extent does incident and persistent use of weak opioids predict problematic opioid use?
- Abstracts
- Is transdermal buprenorphine for chronic non-malignant pain used long term without co-medication with other potentially addictive drugs?
- Abstracts
- Prostaglandin E2 production in synovial tissue and acute postoperative pain after knee arthroscopy
- Abstracts
- Girl presenting with oesophageal spasm pain after fundoplication
- Abstracts
- Epidemiology of persistent postoperative pain: Association of persistent pain and sensory abnormalities
- Abstracts
- Cost–benefit of a 13-week multidiciplinary rehabilitation course for chronic non-malignant pain patients
- Abstracts
- A novel and effective treatment modality for medically unexplained pain
- Abstracts
- Somatocognitive therapy in the management of chronic gynaecological pain. A review of current approach and historical background
- Abstract
- The Manual Intervention Trial (MINT)—The effect of various combinations of naprapathic manual therapy. The study protocol of a randomized controlled trial
- Abstracts
- The experience of chronic pain, loss and grief
- Abstracts
- Effect of buprenorphine and fentanyl in experimental induced superficial, deep and hyperalgesic pain
- Abstract
- Pretreatment with opioids enhances afferent induced long-term potentiation in the rat dorsal horn
- Abstracts
- Pigs in pain—Porcine behavioural responses towards mechanical nociceptive stimulation directed at the hind legs
- Abstracts
- A human experimental bone pain model
