PROGRESSIVE TACTILE HYPERSENSITIVITY - AN INFLAMMATION-INDUCED INCREMENTAL INCREASE IN THE EXCITABILITY OF THE SPINAL-CORD

Two established phenomena contribute to the generation of post-injury pain hypersensitivity: peripheral sensitization, an increase in transd uction sensitivity of high threshold A delta and C-fibre nociceptors, and central sensitization, an increase in excitability of neurones in the spinal cord triggered exclusively by C-fibre inputs. We now descri be a novel phenomenon: progressive tactile hypersensitivity, which con tributes to a cumulative allodynia during inflammation. Behavioural me asurements in conscious intact animals showed that repeated light touc h stimuli delivered at 5-min intervals to an inflamed paw, established 48 h earlier by an intra-plantar injection of complete Freund's adjuv ant (CFA), resulted in a progressive reduction in the mechanical withd rawal threshold by more than 75%, from its already hypersensitive basa l level. This hypersensitive state persisted for several hours after d iscontinuing the touch stimuli and did not occur in non-inflamed anima ls. To monitor nociceptive processing and the afferent fibres responsi ble, we also measured activity in posterior biceps femoris/semitendino sus flexor motor neurones. In non-inflamed decerebrate-spinal rats, th e cutaneous mechanical threshold and pinch-evoked activity of these ne urones are stable when tested repeatedly at 5-min intervals and are ch aracterised by absent or small responses to low intensity mechanical s timuli or electrical activation of A beta-fibres. In inflamed animals, the spontaneous activity, touch-, pinch- and A beta-afferent-evoked r esponses of hamstring flexor motor neurones are significantly increase d. The flexor reflex becomes, moreover, progressively more sensitized by repetition every 5 min, of standard mechanical stimuli (touch and p inch), that do not modify excitability in control non-inflamed animals . A cumulative increase in A beta-afferent-evoked responses also occur s when the test stimulus only comprises stimulation of the sural nerve at A beta strength (10 Hz, 10 sec), showing that A beta-afferents hav e the capacity to produce progressive hypersensitivity. Progressive hy persensitivity, measured here as a progressive tactile allodynia after inflammation in either intact or decerebrate-spinal rats, with its gr adual build-up and contribution from A beta fibres, is very different from the central sensitization induced by C-fibre stimulation which is characterised by a peak increase in excitability soon after the condi tioning input followed by a steady decrement to baseline levels. Progr essive hypersensitivity is likely to be the consequence of an alterati on in the function and phenotype of afferents innervating inflamed tis sue and the pattern of excitation they produce in spinal neurones. The phenomenon may have an important role in the development of inflammat ory pain and hypersensitivity.