Pharmacological pain research
Research in our group concerns the effects of protracted pain, stress, electric stimulation and medication.
Projects
Neurotransmission in nociceptive and antinociceptive neuronal pathways and in the limbic system
The objectives of the project is to study transmitter mechanisms, and the plasticity in neuronal systems in the spinal cord and brain, which modulate pain and reactions to stress. The understanding of these mechanisms may provide a basis for the development of new analgesic drugs.
In previous studies, acute systemic treatment with morphine or selective serotonin uptake inhibitors was found to increase the tissue level and release of substance P (SP) in the periaqueductal grey (PAG), a region involved in pain modulation. Local administration of morphine in the PAG was also found to increase the neurotensin release in this region.
A release of these peptides in the PAG may activate descending pain inhibitory pathways and could be a mechanism involved in opioid analgesia. Moderate acute stress stimuli were also found to induce rapid and selective changes in the tissue levels and/or release of SP, cholecystokinin (CCK) in brain regions such as the PAG and the cingulate cortex - a region recently implicated to be involved in the affective component of pain. These effects may be of importance for the adaptation to stress and stress induced analgesia.
In contrast to the neuropeptides, the extracellular level of the inhibitory transmitter gamma-aminobutyric acid (GABA) in the PAG of the rat was decreased by morphine treatment. A similar effect was seen after spinal cord stimulation (SCS), a method used for the treatment of certain pain syndromes in man. An inhibition of tonic GABA release in the PAG is likely to lead to a disinhibition of the descending pain inhibitory pathways and may thus contribute to opioid and SCS induced analgesia.
In the spinal cord, on the other hand, reduced levels of GABA were found in animals with neurogenic pain and SCS was found to increase the GABA release in individuals that responded to SCS with decreased pain related behaviour.
Methods
In ongoing studies we use intraarticular injection of carrageenan to induce monoarthritis. A method for objective assessment of the increased nociception, by measurement of the weight bearing of the hind paws, is currently evaluated for the monitoring of effects of analgesic drugs. Unilateral partial ligation or complete section of the sciatic nerve is used as models of chronic neurogenic pain and the degree of mechanical allodynia determined.
In these models of chronic pain we study drug effects on transmitter release and pain related behaviour. In a new project in collaboration with several other groups, mechanisms involved in the development of long-term potentiation in wide dynamic range dorsal horn cells will be studied. The hypothesis is that this type of longlasting increase in sensitivity after a painful stimulus to a peripheral nerve may be of importance in a development of chronic pain.
Selected publications
Spinal astrocytes in pain processing: non-neuronal cells as therapeutic targets.
Svensson CI, Brodin E
Mol. Interv. 2010 Feb;10(1):25-38
Prenatal exposure to nicotine affects substance p and preprotachykinin-A mRNA levels in newborn rat.
Berner J, Ringstedt T, Brodin E, Hökfelt T, Lagercrantz H, Wickström R
Pediatr. Res. 2008 Dec;64(6):621-4
Spontaneous nociceptive behaviour in female mice with Freund's complete adjuvant- and carrageenan-induced monoarthritis.
Heilborn U, Berge OG, Arborelius L, Brodin E
Brain Res. 2007 Apr;1143():143-9
Arthritis-induced increase in cholecystokinin release in the rat anterior cingulate cortex is reversed by diclofenac.
Heilborn U, Rost BR, Arborelius L, Brodin E
Brain Res. 2007 Mar;1136(1):51-8