Temporal processes of formalin pain: differential role of the cingulum bundle, fornix pathway and medial bulboreticular formation

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Abstract
Subcutaneous injection of formalin produces a characteristic biphasic pain response. An early phase develops in the first 5 min after injection; the pain then decreases for 10–15 min, followed by a gradual rise to a stable plateau that lasts about 1 h. Rats were injected with 1 μ1 of 2% lidocaine or saline into the anterior cingulum bundle at 0 (immediately), 10 or 30 min prior to formalin injection, or 10, 20 or 30 min after formalin injection, and tested for analgesia in the late phase of the formalin test, 30–70 min after formalin injection. A time-dependent increase in analgesia was obtained when lidocaine was injected into the cingulum at periods ranging from 10 to 30 min after formalin injection, reflecting an anaesthetic duration of less than 20 min. When lidocaine was injected 0 or 10 min prior to formalin injection, a time-dependent increase in analgesia in the late phase was again observed. In these groups, lidocaine should have blocked cingulum activity during the early but not the late phase. The role of the fornix pathway and the medial bulboreticular formation in mediating formalin pain was also examined. Lidocaine produced analgesia in the late phase when injected into the fornix prior to formalin injection but had no effect when adminstered after it. In contrast, when lidocaine was injected into the medial bulboreticular formation it produced analgesia in the late phase when administered after formalin injection, but not prior to it. Taken together, these results suggest that the late pain response to formalin is in part dependent upon plasticity in the central nervous system which occurs during the transient early phase.