Conditioned reflexes are considered engraved memory control functions linking sensory input of afferent nervous system with motor output of efferent signals. Associative memory is a very efficient and fast mechanism enabling living beings to react fast and appropriately to changing environmental conditions. An overwhelming majority of our experiences stored within the memory is well matched and optimally responds to daily living conditions. Some conditioned reflexes, however, may cause inappropriate or pathological reactions. Chronic pain, for example, without underlying anatomical disorders is considered a pathological control function. An interaction between afferent sensor input and efferent motor output is postulated to form a reflex-like response. Accordingly, a circulus vitiosus of pain sensation and muscle and/or vessel contraction is generated when pain becomes chronic.
Learning model of reflex functions on the concept of engrams
The term associative
pain memory reflects the fact that pain generates its own associative memory effect, linking pain-specific sensory inputs to particular motor outputs as sketched in Fig. 1.
If we consider, for example, pain sensation in the shoulder, consequently, shoulder muscles contract for pain relief by aid of protective posture. The modified muscle tonus causes reduction of blood circulation and metabolism in that particular area, which in turn may induce additional pain. If this reflex bow lasts significantly long or if it is very intense, pain sensation and contracted muscles are linked and engraved as an associative pair of items. Whenever a pain sensation is present, the muscle tonus is affected and vice versa. Thus, a feedback loop with positive reverberation is established. The linking memory effect is located somewhere on the nervous pathway in between sensor input and motor output depending on the involved nervous structure Fig. 2.
As known from learning experiments in general, it is assumed that memory effects are based on modifications of the synaptic junctions between nervous cell ensembles within the CNS. Storing information in the long-term memory, usually, requires strong and repeated stimulation of the involved neurons on different hierarchic levels of the CNS. The result of such a successful learning procedure is considered an engram.
This type of associative memory is a basic factor for the enormous efficiency of the human brain.
The type of chronic pain we are interested in is considered to be stored as an engram in the above-mentioned sense. Pain signals modify an ensemble of nerve cells of the peripheral nervous system (PNS) as well as in the central nervous system (CNS), forming a pain memory for this specific pain sensation which, in turn, links a dedicated motor response to the effecting organs such as muscles and vessels (Fig. 3).
The hypothesis of this paper can be described as follows:
When acute pain develops into chronic pain, sensor input and motor output are stored associatively in the PNS and/or CNS and act in a feedback type circle.
From that particular point of time on, the cause of that (chronic) pain has shifted from the organ itself to higher levels of the PNS or CNS. Consequently, successful treatment regimes must affect the pathological reflex bow and erase the particular memory instead of modifying the organ itself.
Information storage by modification of synapses
Nerve signals are transmitted by means of action potentials along axons and chemical substances within the synaptic junctions. If the signals are strong enough or if many adjacent synapses are releasing transmitter substances from their vesicles simultaneously, the contacted nerve cell in turn will fire subsequent electrical signals. They propagate via the axons to succeeding nerve cells. This may result in the appropriate reaction of the muscles in order to get rid of the primary pain. For example, a person may touch the flame of a burning candle and retract the finger to get out of this painful situation. This is considered as a “normal” reaction. In some cases, however, the painful situation may continue for quite a while so that the involved synaptic junctions may be activated in a repeat manner. It is well known that frequently activated synapses transmit signals with a lower threshold so that after the “training or learning process” even very small inputs may activate the following cells. The synaptic strength of particular synapses is increased (long-term potentiation, LTP). Thus, a reflex bow of connecting sensor input (pain) with a specific motor response (muscle or vessel contraction) is established. Trained sequences of (afferent) sensation and (efferent) motor response are the basis of all trained skills. It becomes a problem only if it develops into a reverberating self-enhancing feedback loop as in chronic pain.
Associative memory and its impact on pain therapy
In cases of chronic pain without organic reasons the theory of associative memory draws the attention away from the painful organ to a higher hierarchic memory level. The organ itself is no longer the region of primary therapeutic interest but the according pain memory located in the modified synaptic structure within the related reflex bow. Direct mechanistic view is replaced by looking at higher control functions of the nervous system and its memory potential. Obviously, this idea leads to a radical change of therapeutic approaches of chronic pain distresses. Therapeutic treatment modalities are no more focused on specific organs under pain but on pain memory. In other words: Pain treatment strategies are directed towards reorganization of the memory structure instead of direct (physical or chemical) modification of the organ.
The existence of memory capabilities in general is obvious in humans and highly developed living beings; however, the knowledge about the underlying mechanism is fragmentary and requires further investigation.
Several brain models were developed to shine some light on the subject and to enhance understanding of memory functions.