Salvinorin A reduces mechanical allodynia and spinal neuronal hyperexcitability induced by peripheral formalin injection.
BACKGROUND
Salvinorin A (SA), the main active component of Salvia Divinorum, is a non-nitrogenous kappa opioid receptor (KOR) agonist. It has been shown to reduce acute pain and to exert potent antinflammatory effects. This study assesses the effects and the mode of action of SA on formalin-induced persistent pain in mice. Specifically, the SA effects on long-term behavioural dysfuctions and changes in neuronal activity occurring at spinal level, after single peripheral formalin injection, have been investigated. Moreover, the involvement of microglial and glial cells in formalin-induced chronic pain condition and in SA-mediated effects has been evaluated.


RESULTS
Formalin induced a significant decrease of mechanical withdrawal threshold at the injected and contralateral paw as well as an increase in the duration and frequency, and a rapid decrease in the onset of evoked activity of the nociceptive neurons 7 days after formalin injection. SA daily treatment significantly reduced mechanical allodynia in KOR and cannabinoid receptor 1 (CB1R) sensitive manner. SA treatment also normalized the spinal evoked activity. SA significantly reduced the formalin-mediated microglia and astrocytes activation and modulated pro and anti-inflammatory mediators in the spinal cord.


CONCLUSIONS
SA is effective in reducing formalin-induced mechanical allodynia and spinal neuronal hyperactivity. Our findings suggest that SA reduces glial activation and contributes in the establishment of dysfunctions associated with chronic pain with mechanisms involving KOR and CB1R. SA may provide a new lead compound for developing anti-allodynic agents via KOR and CB1R activation.
Department of Experimental Medicine, Section of Pharmacology, The Second University of Naples, Naples, Italy. francesca-guida@libero.it
Francesca
F
Guida
Livio
L
Luongo
Gabriella
G
Aviello
Enza
E
Palazzo
Maria
M
De Chiaro
Luisa
L
Gatta
Serena
S
Boccella
Ida
I
Marabese
Jordan K
JK
Zjawiony
Raffaele
R
Capasso
Angelo A
AA
Izzo
Vito
V
de Novellis
Sabatino
S
Maione
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D045785:Diterpenes, Clerodane / Q000627:therapeutic use*; D005557:Formaldehyde / Q000633:toxicity; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000188:drug therapy*; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D045785:Diterpenes, Clerodane; D005557:Formaldehyde; C090499:salvinorin A