Table 3 Targets for interference with LTP consolidation and modification of established LTP.
From: Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy
| Â | Â | Â | Â | Â | Â | Â | Â | Start of drug application | Â | Â | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|  | Target | Substance | Action at target | HFS | LFS | in vivo | in vitro | Before LTP induction | During early phase (0-2 h) | During late phase (≥ 3 h) | Effect on L-LTP (unless stated otherwise) | Comments | References |
NMDAR | NMDAR | MK 801, ketamine | antagonist | • |  | • |  |  | • |  | 0 |  | |
VGCC | α2δ-subunit | Gabapentin |  | • |  | • |  |  | • |  | X/? (E-LTP/L-LTP) |  | [65] |
NK1R | NK1R | RP67580, 703,606 | antagonist | • |  | • |  |  | • |  | 0 |  | [3] |
GABAAR | GABAAR | 3-APSA | agonist | • |  | • |  |  | • |  | X/0 (E-LTP/L-LTP) |  | [70] |
|  | GABAAR | Diazepam*, midazolam | Current amplifier | • |  | • |  |  | • | • | X | Depression not reversed by bicuculline | [70] |
Opioid receptors | μ-opioid receptors | Morphine | agonist | • |  | • |  |  | • |  | X/? (E-LTP/L-LTP) |  | [65] |
Descending inhibition | α2-adrenergic receptor | Clonidine | agonist | • |  | • |  |  | • | • | X | Biphasic depression | [90] |
|  | D1/D5 dopamine receptor | SCH 23390 | antagonist | • |  | • |  | • |  |  | X |  | [91] |
Anaesthetic gases |  | Isoflurane |  | • | • | • |  | • |  |  | 0 | Drug present during entire experiment | |
NO-pathway | NOS | L-NAME | inhibitor | • |  | • |  |  | • |  | 0 | Deep dorsal horn | [29] |
|  | extracellular NO | hemoglobin | scavenger | • |  | • |  |  | • |  | 0 |  | [29] |
|  | sGC | ODQ | inhibitor | • |  | • |  |  | • |  | 0 |  | [29] |
|  | mono-, poly- ADRPT | Benzamide | inhibitor | • |  | • |  | • |  |  | X |  | [29] |
Adenosine receptors | A1 receptor | Cyclopentyladenosine | agonist | • |  | • |  |  | • |  | X | Superficial/deep dorsal horn. Drug inhibits LTP at both A-fibre and C-fibre synapses | [142] |
Neurotrophins | TrkB receptor | K252a, TrkB- Fc | Trk inhibitor, BNDF scavenger | • | • | • |  | • |  |  | 0/X | Blocks development of L-LTP in response to LFS but not HFS | [140] |
EphR-ephrin signalling | EphB R | EphB1-Fc | antagonist | • |  | • |  |  | • |  | 0 |  | [102] |
|  | EphB R | EphrinB1-Fc | agonist | • |  | • |  | • |  |  | 0 |  | [102] |
Signal transduction pathways | CaMKII | KN-93, AIP, NK-62 | inhibitor | • |  | • |  | • | • |  | X/0 | Drugs inhibit LTP when administered at 60 min but not at 3 h after LTP induction | [143] |
|  | PKA | Rp-CPT- cAMPS | inhibitor | • |  | • |  |  | • |  | X/0 | Drugs inhibit LTP when administered 15 min but not 30 min after LTP induction | [143] |
|  | PKC | Chelerythrine, Gö 6983 | inhibitor | • |  | • |  |  | • |  | X/0 |  | [143] |
|  | MEK (ERK phosphorylation) | PD 98059 | inhibitor | • |  | • |  |  | • |  | X/0 |  | [110] |
|  | Protein synthesis | Anisomycin, cycloheximide | inhibitor | • |  | • |  | • |  |  | X |  | [133] |
Counterirritation |  | Prologed Aδ-fibre burst stimulation |  | • |  | • |  |  | • |  | X/0 (E-LTP/L-LTP) |  | [144] |
|  |  |  |  | • |  | • |  |  |  | • | Potentiation |  | [144] |
|  |  | Repeated Aδ-fibre burst stimulation |  | • |  | • |  | • | • | • | X/? (E-LTP/L-LTP) | Cumulative depression | [36] |