This work analyzes the role of
cholecystokinin (
CCK) receptors,
dynorphin A₁₋₁₇ and descending facilitation originated in the rostral ventromedial medulla (RVM) on secondary
allodynia and
hyperalgesia in
formalin-injected rats.
Formalin injection (50 μL, 1%, s.c.) produced acute nociception (lasting 1 h) and long-term secondary
allodynia and
hyperalgesia in ipsilateral and contralateral hind paws (lasting 1-12 days). Once established, intra-RVM administration of
lidocaine at day 6, but not at 2, reversed secondary
allodynia and
hyperalgesia in rats. The injection of
YM022 (CCK₂ receptor antagonist), but not
lorglumide (CCK₁ receptor antagonist), into the RVM or spinal cord reversed both nociceptive behaviors. Pre-treatment with
lidocaine,
lorglumide or
YM022 did not prevent the development of secondary
allodynia or
hyperalgesia regardless of the administration route.
Formalin injection increased
dynorphin content in the dorsal, but not the ventral, spinal cord sections at day 6. Moreover, intrathecal administration of
dynorphin antiserum reversed, but was unable to prevent, secondary
allodynia and
hyperalgesia in both hind paws. These results suggest that
formalin-induced secondary
allodynia and
hyperalgesia are maintained by activation of descending facilitatory mechanisms which are dependent on CCK₂ receptors located in the RVM and spinal cord. In addition, data suggest that spinal
dynorphin A₁₋₁₇ and CCK play an important role in
formalin-induced secondary
allodynia and
hyperalgesia.