the-monoiodoacetate-model-of-osteoarthritis-pain-in-the-mouse

The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse

A major symptom of patients with osteoarthritis (OA) is pain that&#160;is triggered by peripheral as well as central changes within the pain pathways. The ...

King's College London

Severe pain is a common and debilitating complication of metastatic bone cancer. Current analgesics provide insufficient pain relief and often lead to significant adverse effects. In models of cancer-induced bone pain, pathological sprouting of sensory fibers at the tumor-bone interface occurs concomitantly with reactive astrocytosis in the dorsal horn of the spinal cord. We observed that calcitonin gene-related peptide (CGRP)-fiber sprouting in the bone was associated with an increase in CGRP content in sensory neuron cell bodies in the dorsal root ganglia (DRG) and increased basal and activity-evoked release of CGRP from their central terminals in the dorsal horn. Intrathecal administration of a peptide antagonist (α-CGRP8-37) attenuated referred allodynia in the hind paw ipsilateral to bone cancer. CGRP receptor components (CLR and RAMP1) were up-regulated in dorsal horn neurons and expressed by reactive astrocytes. In primary cultures of astrocytes, CGRP incubation led to a concentration-dependent increase of forskolin-induced cAMP production, which was attenuated by pretreatment with CGRP8-37. Furthermore, CGRP induced ATP release in astrocytes, which was inhibited by CGRP8-37. We suggest that the peripheral increase in CGRP content observed in cancer-induced bone pain is mirrored by a central increase in the extracellular levels of CGRP. This increase in CGRP not only may facilitate glutamate-driven neuronal nociceptive signaling but also act on astrocytic CGRP receptors and lead to release of ATP.

Thomas Pitcher

Wolfson Centre for Age Related Diseases

King's College London

The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse