central monoamines

1. inhibit nociception

1. facilitate nociception

1. periphery-pronociceptive
2. spinal cord-antinociceptive

Anmerkungen:

• A1-A7

1. At spinal level
   1. Alpha1

      Anmerkungen:

      • excitatory via phospholipase C- increased PI and DAG
   2. Alpha2

      Anmerkungen:

      • inhibition of adenylyl cyclase- decrease cAMP- like opiod receptors>> main focus because they mimic opiods
   3. Beta

      Anmerkungen:

      • excitation via increase cAMP
2. Phrmacology
   1. intrathecal drugs

      Anmerkungen:

      • injected in the CSF of the spinal cord
      1. allpha-adrenoceptor anta
         1. blocks Locus coereleus (LC) evoked analgesia
         2. blocks PAG/RVM evoked analgesia
      2. NA agonists
         1. via alpha2 receptors
            1. in rats
            2. in humans
            3. analgesic effects
         2. side effects
            1. hypotension
            2. sedation

1. electrical or chemical
2. LC, A7- antinociceptive

1. stimulation of pontine N
   1. electrical
   2. chemical
2. recording LC neurons
3. Lesions
   1. electrical of LC
   2. chemical
4. antagonists
   1. alpha1/2
5. knockouts of alpha2 receptors
6. Vital targeting

1. alpha agonists
2. NA re-uptake inhibitors

1. endogenous analgesia