central monoamines

1. inhibit nociception

1. facilitate nociception

1. periphery-pronociceptive
2. spinal cord-antinociceptive

Nota:

• A1-A7

1. At spinal level
   1. Alpha1

      Nota:

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

      Nota:

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

      Nota:

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

      Nota:

      • 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