Partial nerve injury is the main cause of causalgiform pain disorders in humans. We present here a novel animal model of this condition. In rats we unilaterally ligated about half of the sciatic nerve high in the thigh. Within a few hours after the operation, and for several months thereafter, the rats developed guarding behavior of the ipsilateral hind paw and licked it often, suggesting the possibility of spontaneous pain. The plantar surface of the foot was evenly hyperesthetic to non-noxious and noxious stimuli. None of the rats autotomized. There was a sharp decrease in the withdrawal thresholds bilaterally in response to repetitive Von Frey hair stimulation at the plantar side. After a series of such stimuli in the operated side, light touch elicited aversive responses, suggesting allodynia to touch. The withdrawal thresholds to CO2 laser heat pulses were markedly lowered bilaterally. Suprathreshold noxious heat pulses elicited exaggerated responses unilaterally, suggesting thermal hyperalgesia. Pin-prick evoked such exaggerated responses bilaterally (mechanical hyperalgesia). In a companion report, we show that these abnormalities critically depend on the sympathetic outflow. Based on the immediate onset and long-lasting perpetuation of similar symptoms, such as touch-evoked allodynia and hyperalgesia, and the resemblance of the contralateral phenomena to 'mirror image' pains in some humans with causalgia, we suggest that this preparation may serve as a model for syndromes of the causalgiform variety that are triggered by partial nerve injury and maintained by sympathetic activity.

A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury

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The induction of pain: an integrative review

Chronic pain has been recognized as pain that persists past normal healing time5 and hence lacks the acute warning function of physiological nociception.35 Usually pain is regarded as chronic when it lasts or recurs for more than 3 to 6 months.29 Chronic pain is a frequent condition, affecting an estimated 20% of people worldwide6,13,14,18 and accounting for 15% to 20% of physician visits.25,28 Chronic pain should receive greater attention as a global health priority because adequate pain treatment is a human right, and it is the duty of any health care system to provide it.4,13

The current version of the International Classification of Diseases (ICD) of the World Health Organization (WHO) includes some diagnostic codes for chronic pain conditions, but these diagnoses do not reflect the actual epidemiology of chronic pain, nor are they categorized in a systematic manner. The ICD is the preeminent tool for coding diagnoses and documenting investigations or therapeutic measures within the health care systems of many countries. In addition, ICD codes are commonly used to report target diseases and comorbidities of participants in clinical research. Consequently, the current lack of adequate coding in the ICD makes the acquisition of accurate epidemiological data related to chronic pain difficult, prevents adequate billing for health care expenses related to pain treatment, and hinders the development and implementation of new therapies.10,11,16,23,27,31,37

Responding to these shortcomings, the International Association for the Study of Pain (IASP) contacted the WHO and established a Task Force for the Classification of Chronic Pain. The IASP Task Force, which comprises pain experts from across the globe,19 has developed a new and pragmatic classification of chronic pain for the upcoming 11th revision of the ICD. The goal is to create a classification system that is applicable in primary care and in clinical settings for specialized pain management.

A major challenge in this process was finding a rational principle of classification that suits the different types of chronic pain and fits into the general ICD-11 framework. Pain categories are variably defined based on the perceived location (headache), etiology (cancer pain), or the primarily affected anatomical system (neuropathic pain). Some diagnoses of pain defy these classification principles (fibromyalgia).

This problem is not unique to the classification of pain, but exists throughout the ICD. The IASP Task Force decided to give first priority to pain etiology, followed by underlying pathophysiological mechanisms, and finally the body site. Developing this multilayered classification was greatly facilitated by a novel principle of assigning diagnostic codes in ICD-11, termed “multiple parenting.” Multiple parenting allows the same diagnosis to be subsumed under more than 1 category (for a glossary of ICD terms refer to Table ​Table1).1). Each diagnosis retains 1 category as primary parent, but is cross-referenced to other categories that function as secondary parents.



Table 1

Glossary of ICD-11 terms.



The new ICD category for “Chronic Pain” comprises the most common clinically relevant disorders. These disorders were divided into 7 groups (Fig. ​(Fig.1):1): (1) chronic primary pain, (2) chronic cancer pain, (3) chronic posttraumatic and postsurgical pain, (4) chronic neuropathic pain, (5) chronic headache and orofacial pain, (6) chronic visceral pain, and (7) chronic musculoskeletal pain. Experts assigned to each group are responsible for the definition of diagnostic criteria and the selection of the diagnoses to be included under these subcategories of chronic pain. Thanks to Bedirhan Ustun and Robert Jakob of the WHO, these pain diagnoses are now integrated in the beta version of ICD-11 (http://id.who.int/icd/entity/1581976053). The Task Force is generating content models for single entities to describe their clinical characteristics. After peer review overseen by the WHO Steering Committee,39 the classification of chronic pain will be voted into action by the World Health Assembly in 2017.



Figure 1

Organizational chart of Task Force, IASP, and WHO interactions. The IASP Task Force was created by the IASP council and its scope defined in direct consultation of the chairs (R.D.T. and W.R.) with WHO representatives in 2012. The Task Force reports to ...




2. Classification of chronic pain
Chronic pain was defined as persistent or recurrent pain lasting longer than 3 months. This definition according to pain duration has the advantage that it is clear and operationalized.

Optional specifiers for each diagnosis record evidence of psychosocial factors and the severity of the pain. Pain severity can be graded based on pain intensity, pain-related distress, and functional impairment.

2.1. Chronic primary pain
Chronic primary pain is pain in 1 or more anatomic regions that persists or recurs for longer than 3 months and is associated with significant emotional distress or significant functional disability (interference with activities of daily life and participation in social roles) and that cannot be better explained by another chronic pain condition. This is a new phenomenological definition, created because the etiology is unknown for many forms of chronic pain. Common conditions such as, eg, back pain that is neither identified as musculoskeletal or neuropathic pain, chronic widespread pain, fibromyalgia, and irritable bowel syndrome will be found in this section and biological findings contributing to the pain problem may or may not be present. The term “primary pain” was chosen in close liaison with the ICD-11 revision committee, who felt this was the most widely acceptable term, in particular, from a nonspecialist perspective.

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A classification of chronic pain for ICD-11.

Peripheral and central mechanisms of cutaneous hyperalgesia.

A model of experimental peripheral neuropathy producing pain-related disorders has recently been described in the rat. The present study aimed to investigate, using a different and quantifiable behavioural approach, the abnormal pain-related sensations in the animals. The neuropathy was produced by 4 ligatures tied loosely around the common sciatic nerve. 6-8 days after surgery, most of the rats exhibited pain-related disorders ipsilateral to the sciatic ligation, which became maximal 2 weeks after surgery. Mechanical noxious stimulation (pinching of the hind paw) revealed hyperalgesia in all the animals. Rats also exhibited allodynia when tested with the vocalization threshold test to paw pressure (mean vocalization thresholds were 65.5 +/- 3.6% of the preoperative control, P less than 0.01, n = 95). Tests using heat (40, 42, 44, 46 degrees C) and cold (10 degrees C) stimulation (immersion of the rat's hind paw in a bath until it was observed to struggle) indicated hyperalgesia to noxious heat (decrease of 30% in the immersion duration (ID) at a temperature of 46 degrees C), and allodynia to non-noxious heat (decrease of 30% in the temperature of the struggle threshold) and to cold stimulation (decrease by 40% in the ID). In addition, the animals showed modifications in the spontaneous postures of the affected hind paw in a natural setting, suggesting a 'spontaneous' pain-related behaviour (the mean 'pain' rating, derived from the technique used for the formalin test and numbered 0-5, was 2.8 +/- 0.4, P less than 0.01, n = 12). Lastly, sensitized responses were observed to mechanical stimulation after thermal stimulation in the non-noxious range applied to the lesioned but not the non-lesioned paw. The time course of pain-related disorders was comparable whatever the behavioural test, with recovery 2 months after surgery. These results clearly show that the neuropathy produces abnormal pain-related disorders in the rat, which are reminiscent of those observed in some human neuropathies.

Further evidence for ‘pain-related’ behaviours in a model of unilateral peripheral mononeuropathy

Publisher Summary A common sensation can become clearly unpleasant but not necessarily painful, as in motion sickness or in the sensation of “air hunger”. This chapter discusses the term that defines this kind of unpleasant sensation, “coenaesthesiopathia”. Visceral pain can arise from a visceral common sensation—that is, sensations from the bladder. The common sensation is the feeling of fullness, accompanied by a desire to micturate. If it is inconvenient to micturate, the desire to do so becomes stronger and unpleasant, but it is still not painful. During severe urinary retention, as occurs in acute urinary bladder obstruction, this unpleasant feeling becomes increasingly painful. The most important visceral sensation is the visceral pain. The stimuli that induce pain in viscera are different from those that induce pain in the somatic structures. This explains why in the past the viscera was considered to be insensitive to pain.

Clinical approach to visceral sensation

Experimental pain in man is important for several reasons: first, it brings a fundamental body of information to the pathophysiology of pain; second, it is useful to clarify and interpret the mechanisms of spontaneous pain; third, it is essential to clinical pharmacology when an assessment of analgesic drugs must be given. In this review experimentally induced pain will be dealt with in two sections: (a) cutaneous pain; (b) deep pain (somatic and visceral).

Experimental pain in man

This paper reviews the historical development of the concepts of ‘sympathy’ of organs and of the sympathetic nervous system. In particular, the afferent function of the sympathetic system is discussed. The attention is focussed on sympathetic reflex dystrophies, known in some European schools as ‘algodystrophies.’ The pathogenic mechanisms of these affections, especially of causalgia, are discussed, considering the importance of peripheral damage to nerves, lateralisation of pain, ‘mirror phenomena,’ and the relationship between peripheral and central mechanisms of pain.

Reflex sympathetic dystrophies and algodystrophies: historical and pathogenic considerations

In a group of 30 subjects suffering from sympathetic reflex dystrophies of the limbs, the sympathetic ganglia of the affected side were blocked with a local anesthetic. Using an original method, we measured the cutaneous pain threshold before the block and at prefixed intervals after the block during a period of 2 days. In all subjects the cutaneous pain threshold showed damped oscillations both in the limb ipsilateral to the block and in the contralateral one. The analysis of these oscillations showed: (a) that the sympathetic control of the cutaneous pain threshold may be exerted through a negative feedback loop (skin-afferent input-CNS-sympathetic output-skin); (b) that the afferent discharge of a limb controls the contralateral sympathetic output through central mechanisms.

Cutaneous pain threshold changes after sympathetic block in reflex dystrophies.

In healthy subjects and in subjects with chronic myofascial pain of one lower limb, the following was measured in both lower limbs: (i) sequential Hoffman (H) reflex, (ii) sequential Achilles tendon (T) reflex, (iii) cutaneous pain threshold determined with electrical stimuli, before, during and after transcutaneous electrical nerve stimulation (TENS). In healthy subjects no significant differences were observed between the pain thresholds of the two limbs. During and after TENS, changes of the reflexes were related to the pain thresholds. In the pathological subjects a significant difference of pain threshold was present between the affected limb and the contralateral one. An important difference between healthy and pathological subjects is not the quality but the quantity of the changes induced by TENS, in the sense that the levels of inhibition and facilitation of the reflexes are more evident in patients with pain. Indeed, TENS induces a reset of sensory and of motor system and a parallel long lasting effect both on sensory and on muscular function, with concomitant pain relief in the pathological subjects.

The effects of non-painful transcutaneous electrical nerve stimulation on cutaneous pain threshold and muscular reflexes in normal men and in subjects with chronic pain

Paolo Procacci

Papers

Clinical approach to visceral sensation

Experimental pain in man

Reflex sympathetic dystrophies and algodystrophies: historical and pathogenic considerations

Cutaneous pain threshold changes after sympathetic block in reflex dystrophies.

The effects of non-painful transcutaneous electrical nerve stimulation on cutaneous pain threshold and muscular reflexes in normal men and in subjects with chronic pain