A Peptide c-Jun N-Terminal Kinase (JNK) Inhibitor Blocks Mechanical Allodynia after Spinal Nerve Ligation: Respective Roles of JNK Activation in Primary Sensory Neurons and Spinal Astrocytes for Neuropathic Pain Development and Maintenance

Abstract

Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (Ͼ3

Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway

“…1). In agreement with previous studies (Khurgel et al, 1996;Rodriguez et al, 2004), L-α-AA produces a marked reduction of GFAP-positive astrocytes in the dorsal horn but has no effect on NeuN-positive spinal neurons (Zhuang et al, 2006a). The anti-allodynic effect of the toxin is reversible, recovering after 3 days (Fig.…”

“…A correlation between GFAP expression and chronic pain has also been identified in other studies Colburn et al, 1999). However, chronic pain can also been suppressed without inhibition of GFAP expression (Zhuang et al, 2006a). It is unclear whether upregulation of GFAP is required or/and sufficient for chronic pain sensitization, but mounting evidence indicates that persistent activation (e.g.…”

“…This reversible effect might be attributed to migration of neighboring astrocytes. Furthermore, intrathecal injection of this astroglial toxin does not alter the basal sensitivity to pain, which indicates that astrocytes might not be essential for mediating basal pain sensitivity (Zhuang et al, 2006a).…”

“…JNK is the least studied member of the MAPK family. Although all three MAPKs are activated in spinal glial cells after nerve injury, they have different patterns: ERK is activated sequentially in microglia and astrocytes, p38 is activated in microglia, whereas JNK is activated persistently in astrocytes (Table 1) (Jin et al, 2003;Zhuang et al, 2005;Zhuang et al, 2006a). Thus, SNL induces a marked increase in pJNK-immunoreactive (IR) cells in the dorsal horn of the injured side (Fig.…”

“…It is unclear whether upregulation of GFAP is required or/and sufficient for chronic pain sensitization, but mounting evidence indicates that persistent activation (e.g. GFAP upregulation) of spinal astrocytes is a unique feature of chronic pain in different animal models following bone cancer (Honore et al, 2000;Mantyh et al, 2002), spinal nerve ligation (SNL) Zhuang et al, 2006a), partial sciatic-nerve ligation , spinal cord injury (Nesic et al, 2006) and adjuvant-induced inflammation . In addition, S100β is also upregulated in the spinal cord after nerve injury.…”