Heme oxygenase type 2 plays a role in formalin-induced nociception
- 1 May 2000
- journal article
- Published by Wolters Kluwer Health in Pain
- Vol. 86 (1), 75-80
- https://doi.org/10.1016/s0304-3959(00)00238-4
Abstract
Although much attention has been focused in recent years on nitric oxide synthase (NOS) as an enzyme intimately involved in many types of nociceptive signaling, the enzyme heme oxygenase (HO) has received little attention. Yet, HO produces gaseous second messenger molecule CO which, like NO, has proven to be an important neurotransmitter in the CNS. In these studies we provide detailed evidence that HO activity is critical to formalin-induced licking behavior in mice. The HO inhibitor tin protoporphyrin (Sn-P) dose-dependently reduced formalin-stimulated licking behavior in both phases of the formalin assay. This apparent analgesic effect was unlikely due to the non-specific effects of this agent as Sn-P did not alter rotarod performance, and the blood-brain barrier impermeant HO inhibitor zinc protoporphyrin (Zn-P) had little effect on licking times. We also hypothesized that heme oxygenase type 2 (HO-2) was the specific isoform of HO involved in nociception. Mice with a targeted disruption of the HO-2 gene were found to have greatly reduced licking times. Furthermore, Sn-P did not further reduce licking times when administered to HO-2 knockout animals. Taken together our evidence indicates that HO plays an important role in nociceptive signaling related to inflammatory-type pain, and that HO-2 is the isozyme mediating this nociception.Keywords
This publication has 30 references indexed in Scilit:
- Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injuryProceedings of the National Academy of Sciences, 1999
- Raised levels of exhaled carbon monoxide are associated with an increased expression of heme oxygenase-1 in airway macrophages in asthma: a new marker of oxidative stressThorax, 1998
- Hyperalgesia in mice lacking the Kv1.1 potassium channel geneNeuroscience Letters, 1998
- Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liverHepatology, 1998
- Oxygen toxicity and iron accumulation in the lungs of mice lacking heme oxygenase-2.JCI Insight, 1998
- Pitfalls using metalloporphyrins in carbon monoxide researchTrends in Pharmacological Sciences, 1997
- Regulation of the second-messenger systems in the rat spinal cord during prolonged peripheral inflammationPain, 1994
- Nitric oxide and carbon monoxide as possible retrograde messengers in hgippocampal long‐term potentiationJournal of Neurobiology, 1994
- Glutathione Depletion Induces Heme Oxygenase‐1 (HSP32) mRNA and Protein in Rat BrainJournal of Neurochemistry, 1993
- A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesiaPain, 1988